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Eddy A. Van der Zee
Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, the Netherlands

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Review
Published: 17 June 2020 in F1000Research
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Vibrations are all around us. We can detect vibrations with sensitive skin mechanoreceptors, but our conscious awareness of the presence of vibrations is often limited. Nevertheless, vibrations play a role in our everyday life. Here, we briefly describe the function of vibration detection and how it can be used for medical applications by way of whole body vibration. Strong vibrations can be harmful, but milder vibrations can be beneficial, although to what extent and how large the clinical relevance is are still controversial. Whole body vibration can be applied via a vibrating platform, used in both animal and human research. Recent findings make clear that the mode of action is twofold: next to the rather well-known exercise (muscle) component, it also has a sensory (skin) component. Notably, the sensory (skin) component stimulating the brain has potential for several purposes including improvements in brain-related disorders. Combining these two components by selecting the optimal settings in whole body vibration has clear potential for medical applications. To realize this, the field needs more standardized and personalized protocols. It should tackle what could be considered the “Big Five” variables of whole body vibration designs: vibration amplitude, vibration frequency, method of application, session duration/frequency, and total intervention duration. Unraveling the underlying mechanisms by translational research can help to determine the optimal settings. Many systematic reviews on whole body vibration end with the conclusion that the findings are promising yet inconclusive. This is mainly because of the large variation in the “Big Five” settings between studies and incomplete reporting of methodological details hindering reproducibility. We are of the opinion that when (part of) these optimal settings are being realized, a much better estimate can be given about the true potential of whole body vibration as a medical application.

ACS Style

Tamás Oroszi; Marieke J.G. Van Heuvelen; Csaba Nyakas; Eddy A. Van Der Zee. Vibration detection: its function and recent advances in medical applications. F1000Research 2020, 9, 619 .

AMA Style

Tamás Oroszi, Marieke J.G. Van Heuvelen, Csaba Nyakas, Eddy A. Van Der Zee. Vibration detection: its function and recent advances in medical applications. F1000Research. 2020; 9 ():619.

Chicago/Turabian Style

Tamás Oroszi; Marieke J.G. Van Heuvelen; Csaba Nyakas; Eddy A. Van Der Zee. 2020. "Vibration detection: its function and recent advances in medical applications." F1000Research 9, no. : 619.

Chapter
Published: 24 May 2020 in Manual of Vibration Exercise and Vibration Therapy
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Vibrations are all around us, but often not consciously perceived by humans in contrast to many other species. What can we learn from the detection and use of vibrations by other species? In this chapter, I set out to illustrate that vibrations are used for several functions in nature, and that the human capacity to detect and utilize vibrations can be traced far beyond our early mammalian ancestors. The existence of a multitude of sensory organs responding to vibrations, with partly overlapping sensitivity to frequencies and varying adaptation speeds, already suggests that somewhere during the evolution of mammals vibrations were important for the interaction between the host and the environment. In addition, it became a crucial modality enabling interactions between individuals (either of the same species or between different species). Vibrations present in our current society may influence our well-being and behavior. Knowledge of the natural origins of vibration detection and their functions can increase our awareness of vibrations, and how it can be employed. This awareness strongly links to the field of whole body vibration, where vibrations are primarily used as an exercise modality. In my opinion, this awareness could contribute to enhance the usefulness and effectiveness of whole body vibration therapies.

ACS Style

Eddy A. Van Der Zee. The Biology of Vibration. Manual of Vibration Exercise and Vibration Therapy 2020, 23 -38.

AMA Style

Eddy A. Van Der Zee. The Biology of Vibration. Manual of Vibration Exercise and Vibration Therapy. 2020; ():23-38.

Chicago/Turabian Style

Eddy A. Van Der Zee. 2020. "The Biology of Vibration." Manual of Vibration Exercise and Vibration Therapy , no. : 23-38.

Review
Published: 22 May 2020 in International Journal of Environmental Research and Public Health
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COVID-19 is a highly infectious respiratory disease which leads to several clinical conditions related to the dysfunction of the respiratory system along with other physical and psychological complaints. Severely affected patients are referred to intensive care units (ICUs), limiting their possibilities for physical exercise. Whole body vibration (WBV) exercise is a non-invasive, physical therapy, that has been suggested as part of the procedures involved with pulmonary rehabilitation, even in ICU settings. Therefore, in the current review, the World Association of Vibration Exercise Experts (WAVEX) reviewed the potential of WBV exercise as a useful and safe intervention for the management of infected individuals with COVID-19 by mitigating the inactivity-related declines in physical condition and reducing the time in ICU. Recommendations regarding the reduction of fatigue and the risk of dyspnea, the improvement of the inflammatory and redox status favoring cellular homeostasis and the overall improvement in the quality of life are provided. Finally, practical applications for the use of this paradigm leading to a better prognosis in bed bound and ICU-bound subjects is proposed.

ACS Style

Borja Sañudo; Adérito Seixas; Rainer Gloeckl; Jörn Rittweger; Rainer Rawer; Redha Taiar; Eddy A. Van Der Zee; Marieke J.G. Van Heuvelen; Ana Cristina Lacerda; Alessandro Sartorio; Michael Bemben; Darryl Cochrane; Trentham Furness; Danúbia De Sá-Caputo; Mario Bernardo-Filho. Potential Application of Whole Body Vibration Exercise for Improving the Clinical Conditions of COVID-19 Infected Individuals: A Narrative Review from the World Association of Vibration Exercise Experts (WAVex) Panel. International Journal of Environmental Research and Public Health 2020, 17, 3650 .

AMA Style

Borja Sañudo, Adérito Seixas, Rainer Gloeckl, Jörn Rittweger, Rainer Rawer, Redha Taiar, Eddy A. Van Der Zee, Marieke J.G. Van Heuvelen, Ana Cristina Lacerda, Alessandro Sartorio, Michael Bemben, Darryl Cochrane, Trentham Furness, Danúbia De Sá-Caputo, Mario Bernardo-Filho. Potential Application of Whole Body Vibration Exercise for Improving the Clinical Conditions of COVID-19 Infected Individuals: A Narrative Review from the World Association of Vibration Exercise Experts (WAVex) Panel. International Journal of Environmental Research and Public Health. 2020; 17 (10):3650.

Chicago/Turabian Style

Borja Sañudo; Adérito Seixas; Rainer Gloeckl; Jörn Rittweger; Rainer Rawer; Redha Taiar; Eddy A. Van Der Zee; Marieke J.G. Van Heuvelen; Ana Cristina Lacerda; Alessandro Sartorio; Michael Bemben; Darryl Cochrane; Trentham Furness; Danúbia De Sá-Caputo; Mario Bernardo-Filho. 2020. "Potential Application of Whole Body Vibration Exercise for Improving the Clinical Conditions of COVID-19 Infected Individuals: A Narrative Review from the World Association of Vibration Exercise Experts (WAVex) Panel." International Journal of Environmental Research and Public Health 17, no. 10: 3650.

Journal article
Published: 19 March 2020 in Alzheimer's Research & Therapy
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Background Potential moderators such as exercise intensity or apolipoprotein-E4 (ApoE4) carriership may determine the magnitude of exercise effects on physical and cognitive functions in patients with dementia (PwD). We determined the effects of a 24-week aerobic and strength training program with a low- and high-intensity phase on physical and cognitive function. Methods In an assessor-blinded randomized trial, 91 PwD (all-cause dementia, recruited from daycare and residential care facilities, age 82.3 ± 7.0 years, 59 women, Mini-Mental State Examination 20.2 ± 4.4) were allocated to the exercise or control group. In the exercise group, PwD participated in a walking and lower limb strength training program with 12 weeks low- and 12 weeks high-intensity training offered three times/week. Attention-matched control participants performed flexibility exercises and recreational activities. We assessed adherence, compliance, and exercise intensity for each session. We assessed physical (endurance, gait speed, mobility, balance, leg strength) and cognitive (verbal memory, visual memory, executive function, inhibitory control, psychomotor speed) functions with performance-based tests at baseline and after 6, 12, 18, 24, and 36 weeks (follow-up). ApoE4 carriership was determined post-intervention. Results Sixty-nine PwD were analyzed. Their mean attendance was ~ 60% during the study period. There were no significant effects of the exercise vs. control intervention on endurance, mobility, balance, and leg strength in favor of the exercise group (Cohen’s d = 0.13–0.18). Gait speed significantly improved with ~ 0.05 m/s after the high-intensity phase for exercise participants (Cohen’s d = 0.41) but declined at follow-up. There were no significant effects of the exercise vs. control intervention on any of the cognitive measures (Cohen’s d ~ − 0.04). ApoE4 carriership did not significantly moderate exercise effects on physical or cognitive function. Conclusions Exercise was superior to control activities for gait speed in our sample of PwD. However, the training effect provided no protection for mobility loss after detraining (follow-up). There were no beneficial effects of the exercise vs. control group on cognitive function. Exercise intensity moderated the effects of exercise on gait speed. ApoE4 carriership moderated the effect of exercise on global cognition only (trend level). Trial registration Netherlands Trial Register, NTR5035. Registered on 2 March 2015.

ACS Style

L. M. J. Sanders; T. Hortobágyi; E. G. A. Karssemeijer; E. A. Van Der Zee; E. J. A. Scherder; M. J. G. Van Heuvelen. Effects of low- and high-intensity physical exercise on physical and cognitive function in older persons with dementia: a randomized controlled trial. Alzheimer's Research & Therapy 2020, 12, 1 -15.

AMA Style

L. M. J. Sanders, T. Hortobágyi, E. G. A. Karssemeijer, E. A. Van Der Zee, E. J. A. Scherder, M. J. G. Van Heuvelen. Effects of low- and high-intensity physical exercise on physical and cognitive function in older persons with dementia: a randomized controlled trial. Alzheimer's Research & Therapy. 2020; 12 (1):1-15.

Chicago/Turabian Style

L. M. J. Sanders; T. Hortobágyi; E. G. A. Karssemeijer; E. A. Van Der Zee; E. J. A. Scherder; M. J. G. Van Heuvelen. 2020. "Effects of low- and high-intensity physical exercise on physical and cognitive function in older persons with dementia: a randomized controlled trial." Alzheimer's Research & Therapy 12, no. 1: 1-15.

Special issue article
Published: 21 January 2020 in European Journal of Neuroscience
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It is widely acknowledged that de novo protein synthesis is crucial for the formation and consolidation of long‐term memories. While the basal activity of many signaling cascades that modulate protein synthesis fluctuate in a circadian fashion, it is unclear whether the temporal dynamics of protein synthesis‐dependent memory consolidation varies depending on the time of day. More specifically, it is unclear whether protein synthesis inhibition affects hippocampus‐dependent memory consolidation in rodents differentially across the day (i.e., the inactive phase with an abundance of sleep) and night (i.e., the active phase with little sleep). To address this question, male and female C57Bl6/J mice were trained in a contextual fear conditioning task at the beginning or the end of the light phase. Animals received a single systemic injection with the protein synthesis inhibitor anisomycin or vehicle directly, 4 hours, 8 hours, or 11.5 hours following training, and memory was assessed after 24 hours. Here, we show that protein synthesis inhibition impaired the consolidation of context‐fear memories selectively when the protein synthesis inhibitor was administered at the first three time points, irrespective of timing of training. Even though the basal activity of signaling pathways regulating de novo protein synthesis may fluctuate across the 24h cycle, these results suggest that the temporal dynamics of protein synthesis‐dependent memory consolidation are similar for day‐time and night‐time learning.

ACS Style

Frank Raven; Youri G. Bolsius; Lara V. Van Renssen; Elroy L. Meijer; Eddy A. Van Der Zee; Peter Meerlo; Robbert Havekes. Elucidating the role of protein synthesis in hippocampus‐dependent memory consolidation across the day and night. European Journal of Neuroscience 2020, 1 .

AMA Style

Frank Raven, Youri G. Bolsius, Lara V. Van Renssen, Elroy L. Meijer, Eddy A. Van Der Zee, Peter Meerlo, Robbert Havekes. Elucidating the role of protein synthesis in hippocampus‐dependent memory consolidation across the day and night. European Journal of Neuroscience. 2020; ():1.

Chicago/Turabian Style

Frank Raven; Youri G. Bolsius; Lara V. Van Renssen; Elroy L. Meijer; Eddy A. Van Der Zee; Peter Meerlo; Robbert Havekes. 2020. "Elucidating the role of protein synthesis in hippocampus‐dependent memory consolidation across the day and night." European Journal of Neuroscience , no. : 1.

Comparative study
Published: 16 October 2019 in Nutrients
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Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in the tyrosine degradation pathway. Neurocognitive deficiencies have been described in TT1 patients, that have, among others, been related to changes in plasma large neutral amino acids (LNAA) that could result in changes in brain LNAA and neurotransmitter concentrations. Therefore, this project aimed to investigate plasma and brain LNAA, brain neurotransmitter concentrations and behavior in C57 Bl/6 fumarylacetoacetate hydrolase deficient (FAH-/-) mice treated with 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (NTBC) and/or diet and wild-type mice. Plasma and brain tyrosine concentrations were clearly increased in all NTBC treated animals, even with diet (p < 0.001). Plasma and brain phenylalanine concentrations tended to be lower in all FAH-/- mice. Other brain LNAA, were often slightly lower in NTBC treated FAH-/- mice. Brain neurotransmitter concentrations were usually within a normal range, although serotonin was negatively correlated with brain tyrosine concentrations (p < 0.001). No clear behavioral differences between the different groups of mice could be found. To conclude, this is the first study measuring plasma and brain biochemistry in FAH-/- mice. Clear changes in plasma and brain LNAA have been shown. Further research should be done to relate the biochemical changes to neurocognitive impairments in TT1 patients.

ACS Style

Willem G. Van Ginkel; Danique Van Vliet; Els Van Der Goot; Martijn H. J. R. Faassen; Arndt Vogel; M. Rebecca Heiner-Fokkema; Eddy. A. Van Der Zee; Francjan J. Van Spronsen. Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice. Nutrients 2019, 11, 2486 .

AMA Style

Willem G. Van Ginkel, Danique Van Vliet, Els Van Der Goot, Martijn H. J. R. Faassen, Arndt Vogel, M. Rebecca Heiner-Fokkema, Eddy. A. Van Der Zee, Francjan J. Van Spronsen. Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice. Nutrients. 2019; 11 (10):2486.

Chicago/Turabian Style

Willem G. Van Ginkel; Danique Van Vliet; Els Van Der Goot; Martijn H. J. R. Faassen; Arndt Vogel; M. Rebecca Heiner-Fokkema; Eddy. A. Van Der Zee; Francjan J. Van Spronsen. 2019. "Blood and Brain Biochemistry and Behaviour in NTBC and Dietary Treated Tyrosinemia Type 1 Mice." Nutrients 11, no. 10: 2486.

Journal article
Published: 19 September 2019 in Nutrients
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Many phenylketonuria (PKU) patients cannot adhere to the severe dietary restrictions as advised by the European PKU guidelines, which can be accompanied by aggravated neuropsychological impairments that, at least in part, have been attributed to brain monoaminergic neurotransmitter deficiencies. Supplementation of large neutral amino acids (LNAA) to an unrestricted diet has previously been shown to effectively improve brain monoamines in PKU mice of various ages. To determine the additive value of LNAA supplementation to a liberalized phenylalanine-restricted diet, brain and plasma monoamine and amino acid concentrations in 10 to 16-month-old adult C57Bl/6 PKU mice on a less severe phenylalanine-restricted diet with LNAA supplementation were compared to those on a non-supplemented severe or less severe phenylalanine-restricted diet. LNAA supplementation to a less severe phenylalanine-restricted diet was found to improve both brain monoamine and phenylalanine concentrations. Compared to a severe phenylalanine-restricted diet, it was equally effective to restore brain norepinephrine and serotonin even though being less effective to reduce brain phenylalanine concentrations. These results in adult PKU mice support the idea that LNAA supplementation may enhance the effect of a less severe phenylalanine-restricted diet and suggest that cerebral outcome of PKU patients treated with a less severe phenylalanine-restricted diet may be helped by additional LNAA treatment.

ACS Style

Danique Van Vliet; Els Van Der Goot; Wiggert G. Van Ginkel; Martijn H. J. R. Van Faassen; Pim De Blaauw; Ido P. Kema; Aurora Martinez; M. Rebecca Heiner-Fokkema; Eddy A. Van Der Zee; Francjan J. Van Spronsen. The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice. Nutrients 2019, 11, 2252 .

AMA Style

Danique Van Vliet, Els Van Der Goot, Wiggert G. Van Ginkel, Martijn H. J. R. Van Faassen, Pim De Blaauw, Ido P. Kema, Aurora Martinez, M. Rebecca Heiner-Fokkema, Eddy A. Van Der Zee, Francjan J. Van Spronsen. The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice. Nutrients. 2019; 11 (9):2252.

Chicago/Turabian Style

Danique Van Vliet; Els Van Der Goot; Wiggert G. Van Ginkel; Martijn H. J. R. Van Faassen; Pim De Blaauw; Ido P. Kema; Aurora Martinez; M. Rebecca Heiner-Fokkema; Eddy A. Van Der Zee; Francjan J. Van Spronsen. 2019. "The Benefit of Large Neutral Amino Acid Supplementation to a Liberalized Phenylalanine-Restricted Diet in Adult Phenylketonuria Patients: Evidence from Adult Pah-Enu2 Mice." Nutrients 11, no. 9: 2252.

Journal article
Published: 01 April 2019 in Neurobiology of Learning and Memory
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Toxic levels of phenylalanine in blood and brain is a characteristic of (untreated) phenylketonuria (PKU), leading to cognitive deficits in PKU mice. In addition, our recent findings showed that PKU mice (as well as PKU patients) have a disturbed sleep/wake cycle. As a consequence, sleep loss may contribute to cognitive deficits in PKU. Sleep loss has been linked to increased activation of microglia in the hippocampus. In this study, we set out to examine morphological features of the microglia population in the hippocampus of the mouse PKU model, using both the C57Bl/6 and the BTBR strain and their wild-type controls (age 5.3 +/- 0.5 months; n=16 per group, both males and females; n=8 each). Microglial activation is reflected by retraction and thickening of the dendritic branches and an increase in cell body size of a microglial cell. Such morphological changes of microglia were studied by way of immunohistochemical staining for Iba-1, a microglia-specific calcium binding protein. We measured the number of microglia in seven subregions of the dorsal hippocampus. The level of microglial activation was determined, based on the ratio between the soma size and total cell size (soma size plus the area covered by the dendritic branches). Results showed subtle but statistical significant activation of hippocampal microglia in the C57Bl6, but not in the BTBR, PKU mice when compared with their wild-type controls. Also the total number of microglia was higher in the C57Bl/6 PKU (compared to the wild-type) mouse, but not in the BTBR PKU mouse. It is concluded that the C57Bl/6 PKU mouse has mildly higher microglia activity, which may support rather than hamper hippocampal homeostasis. The results further indicate that high levels of phenylalanine or disturbed sleep patterns do not consequently cause hippocampal microglial activation in the PKU mouse. It is currently unknown why the two PKU mouse strains show these differences in number and activation level of their hippocampal microglia, and to what extent it influences hippocampal functioning. Further scrutinizing the role of microglia functioning in the context of PKU is therefore warranted.

ACS Style

Els van der Goot; Vibeke M. Bruinenberg; Femke M. Hormann; Ulrich L.M. Eisel; Francjan J. van Spronsen; Eddy A. Van der Zee. Hippocampal microglia modifications in C57Bl/6 Pah and BTBR Pah phenylketonuria (PKU) mice depend on the genetic background, irrespective of disturbed sleep patterns. Neurobiology of Learning and Memory 2019, 160, 139 -143.

AMA Style

Els van der Goot, Vibeke M. Bruinenberg, Femke M. Hormann, Ulrich L.M. Eisel, Francjan J. van Spronsen, Eddy A. Van der Zee. Hippocampal microglia modifications in C57Bl/6 Pah and BTBR Pah phenylketonuria (PKU) mice depend on the genetic background, irrespective of disturbed sleep patterns. Neurobiology of Learning and Memory. 2019; 160 ():139-143.

Chicago/Turabian Style

Els van der Goot; Vibeke M. Bruinenberg; Femke M. Hormann; Ulrich L.M. Eisel; Francjan J. van Spronsen; Eddy A. Van der Zee. 2019. "Hippocampal microglia modifications in C57Bl/6 Pah and BTBR Pah phenylketonuria (PKU) mice depend on the genetic background, irrespective of disturbed sleep patterns." Neurobiology of Learning and Memory 160, no. : 139-143.

Research article
Published: 15 March 2019 in PLOS ONE
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In phenylketonuria (PKU), a gene mutation in the phenylalanine metabolic pathway causes accumulation of phenylalanine (Phe) in blood and brain. Although early introduction of a Phe-restricted diet can prevent severe symptoms from developing, patients who are diagnosed and treated early still experience deficits in cognitive functioning indicating shortcomings of current treatment. In the search for new and/or additional treatment strategies, a specific nutrient combination (SNC) was postulated to improve brain function in PKU. In this study, a long-term dietary intervention with a low-Phe diet, a specific combination of nutrients designed to improve brain function, or both concepts together was investigated in male and female BTBR PKU and WT mice. 48 homozygous wild-types (WT, +/+) and 96 PKU BTBRPah2 (-/-) male and female mice received dietary interventions from postnatal day 31 till 10 months of age and were distributed in the following six groups: high Phe diet (WT C-HP, PKU C-HP), high Phe plus specific nutrient combination (WT SNC-HP, PKU SNC-HP), PKU low-Phe diet (PKU C-LP), and PKU low-Phe diet plus specific nutrient combination (PKU SNC- LP). Memory and motor function were tested at time points 3, 6, and 9 months after treatment initiation in the open field (OF), novel object recognition test (NOR), spatial object recognition test (SOR), and the balance beam (BB). At the end of the experiments, brain neurotransmitter concentrations were determined. In the NOR, we found that PKU mice, despite being subjected to high Phe conditions, could master the task on all three time points when supplemented with SNC. Under low Phe conditions, PKU mice on control diet could master the NOR at all three time points, while PKU mice on the SNC supplemented diet could master the task at time points 6 and 9 months. SNC supplementation did not consistently influence the performance in the OF, SOR or BB in PKU mice. The low Phe diet was able to normalize concentrations of norepinephrine and serotonin; however, these neurotransmitters were not influenced by SNC supplementation. This study demonstrates that both a long-lasting low Phe diet, the diet enriched with SNC, as well as the combined diet was able to ameliorate some, but not all of these PKU-induced abnormalities. Specifically, this study is the first long-term intervention study in BTBR PKU mice that shows that SNC supplementation can specifically improve novel object recognition.

ACS Style

Vibeke M. Bruinenberg; Danique Van Vliet; Els Van Der Goot; Danielle S. Counotte; Mirjam Kuhn; Francjan J. Van Spronsen; Eddy A. Van Der Zee. Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU). PLOS ONE 2019, 14, e0213391 .

AMA Style

Vibeke M. Bruinenberg, Danique Van Vliet, Els Van Der Goot, Danielle S. Counotte, Mirjam Kuhn, Francjan J. Van Spronsen, Eddy A. Van Der Zee. Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU). PLOS ONE. 2019; 14 (3):e0213391.

Chicago/Turabian Style

Vibeke M. Bruinenberg; Danique Van Vliet; Els Van Der Goot; Danielle S. Counotte; Mirjam Kuhn; Francjan J. Van Spronsen; Eddy A. Van Der Zee. 2019. "Long-term dietary intervention with low Phe and/or a specific nutrient combination improve certain aspects of brain functioning in phenylketonuria (PKU)." PLOS ONE 14, no. 3: e0213391.

Research article
Published: 01 October 2018 in Dose-Response
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The biological consequences of mechanical whole body vibration (WBV) on the brain are not well documented. The aim of the current study was to further investigate the effects of a 5-week WBV intervention on brain functions. Mice (C57Bl/6J males, age 15 weeks) were exposed to 30 Hz WBV sessions (10 minutes per day, 5 days per week, for a period of 5 weeks; n = 10). Controls received the same intervention without the actual vibration (n = 10). Humans (both genders, age ranging from 44-99 years) were also exposed to daily sessions of 30 Hz WBV (4 minutes per day, 4 days per week, for a period of 5 weeks; n = 18). Controls received the same protocol using a 1 Hz protocol (n = 16). Positron emission tomography imaging was performed in the mice, and revealed that glucose uptake was not changed as a consequence of the 5-week WBV intervention. Whole body vibration did, however, improve motor performance and reduced arousal-induced home cage activity. Cognitive tests in humans revealed a selective improvement in the Stroop Color-Word test. Taken together, it is concluded that WBV is a safe intervention to improve brain functioning, although the subtle effects suggest that the protocol is as yet suboptimal.

ACS Style

Ate S. Boerema; Marelle Heesterbeek; Selma A. Boersma; Regien Schoemaker; Erik de Vries; Marieke J. G. Van Heuvelen; Eddy A. Van Der Zee. Beneficial Effects of Whole Body Vibration on Brain Functions in Mice and Humans. Dose-Response 2018, 16, 1 .

AMA Style

Ate S. Boerema, Marelle Heesterbeek, Selma A. Boersma, Regien Schoemaker, Erik de Vries, Marieke J. G. Van Heuvelen, Eddy A. Van Der Zee. Beneficial Effects of Whole Body Vibration on Brain Functions in Mice and Humans. Dose-Response. 2018; 16 (4):1.

Chicago/Turabian Style

Ate S. Boerema; Marelle Heesterbeek; Selma A. Boersma; Regien Schoemaker; Erik de Vries; Marieke J. G. Van Heuvelen; Eddy A. Van Der Zee. 2018. "Beneficial Effects of Whole Body Vibration on Brain Functions in Mice and Humans." Dose-Response 16, no. 4: 1.

Study protocol
Published: 14 August 2018 in BMC Geriatrics
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Dementia affects cognitive functioning, physical functioning, activities of daily living (ADLs), and quality of life (QOL). Pharmacological treatments to manage, cure or prevent dementia remain controversial. Therefore development of non-pharmacological approaches to prevent, or at least delay the onset and progression of dementia is urgently needed. Passive exercise is proposed to be such a non-pharmacological alternative. This study primarily aims to investigate the effects of three different forms of passive exercise on QOL and ADLs of institutionalized patients with dementia. The secondary aims are to assess the effects of three different forms of passive exercise on cognitive functioning and physical functioning of institutionalized patients with dementia as well as on care burden of both the primary formal and primary informal caregivers of these patients. This is a multicenter randomized controlled trial. Three forms of passive exercise are distinguished; motion simulation (MSim), whole body vibration (WBV), and a combination of both MSim + WBV. Intervention effects are compared to a control group receiving regular care. Institutionalized patients with dementia follow a six-week intervention program consisting of four 4-12 min sessions a week. The primary outcome measures QOL and ADLs and secondary outcome measure care burden are assessed with questionnaires filled in by the primary formal and informal caregivers of the patient. The other secondary outcome measures cognitive and physical functioning are assessed by individual testing. The four groups are compared at baseline, after 6 weeks of intervention, and 2 weeks after the intervention has ended. This study will provide insight in the effects of different forms of passive exercise on QOL, ADLs, cognitive and physical functioning and care burden of institutionalized patients with dementia and their primary formal and informal caregivers. The results of this study might support the idea that passive exercise can be an efficient alternative for physical activity for patients not able to be or stay involved in active physical exercise. The Netherlands National Trial Register ( NTR6290 ). Retrospectively registered 29 March 2017.

ACS Style

Marelle Heesterbeek; Eddy A. Van Der Zee; Marieke J. G. Van Heuvelen. Passive exercise to improve quality of life, activities of daily living, care burden and cognitive functioning in institutionalized older adults with dementia - a randomized controlled trial study protocol. BMC Geriatrics 2018, 18, 182 .

AMA Style

Marelle Heesterbeek, Eddy A. Van Der Zee, Marieke J. G. Van Heuvelen. Passive exercise to improve quality of life, activities of daily living, care burden and cognitive functioning in institutionalized older adults with dementia - a randomized controlled trial study protocol. BMC Geriatrics. 2018; 18 (1):182.

Chicago/Turabian Style

Marelle Heesterbeek; Eddy A. Van Der Zee; Marieke J. G. Van Heuvelen. 2018. "Passive exercise to improve quality of life, activities of daily living, care burden and cognitive functioning in institutionalized older adults with dementia - a randomized controlled trial study protocol." BMC Geriatrics 18, no. 1: 182.

Comparative study
Published: 01 April 2018 in Journal of Neuroscience Methods
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Burrowing qualifies as a suitable voluntary strength training method in mice. Furthermore, resistance running shares features of strength training and endurance (aerobic) exercise and should be considered a multi-modal aerobic-strength exercise method in mice.

ACS Style

P. Roemers; P.N. Mazzola; P.P. De Deyn; W.J. Bossers; M.J.G. Van Heuvelen; E.A. Van Der Zee. Burrowing as a novel voluntary strength training method for mice: A comparison of various voluntary strength or resistance exercise methods. Journal of Neuroscience Methods 2018, 300, 112 -126.

AMA Style

P. Roemers, P.N. Mazzola, P.P. De Deyn, W.J. Bossers, M.J.G. Van Heuvelen, E.A. Van Der Zee. Burrowing as a novel voluntary strength training method for mice: A comparison of various voluntary strength or resistance exercise methods. Journal of Neuroscience Methods. 2018; 300 ():112-126.

Chicago/Turabian Style

P. Roemers; P.N. Mazzola; P.P. De Deyn; W.J. Bossers; M.J.G. Van Heuvelen; E.A. Van Der Zee. 2018. "Burrowing as a novel voluntary strength training method for mice: A comparison of various voluntary strength or resistance exercise methods." Journal of Neuroscience Methods 300, no. : 112-126.

Original research article
Published: 26 April 2017 in Frontiers in Neurology
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Sleep problems have not been directly reported in Phenylketonuria (PKU). In PKU, the metabolic pathway of phenylalanine is disrupted, which, among others, causes deficits in the neurotransmitters and sleep modulators dopamine, norepinephrine and serotonin. Understanding sleep problems in PKU patients may help explain the pathophysiology of brain dysfunction in PKU patients. In this explorative study we investigated possible sleep problems in adult treated PKU patients and untreated PKU mice. In the PKU patients, sleep characteristics were compared to healthy first degree relatives by assessment of sleep disturbances, sleep-wake patterns, and sleepiness with the help of four questionnaires: Holland sleep disorder questionnaire, Pittsburgh sleep quality index, Epworth sleepiness scale, and Munich Chronotype Questionnaire. The results obtained with the questionnaires show that PKU individuals suffer more from sleep disorders, a reduced sleep quality, an increased latency to fall asleep, and experience more sleepiness during the day. In the PKU mice, activity patterns were recorded with passive infrared recorders. PKU mice switched more often between active and non-active behavior and shifted a part of their resting behavior into the active period, confirming that sleep quality is affected as a consequence of PKU. Together, these results give the first indication that sleep problems are present in PKU. More detailed future research will give a better understanding of these problems which could ultimately result in the improvement of treatment strategies by including sleep quality as an additional treatment target.

ACS Style

Vibeke M. Bruinenberg; Marijke C. M. Gordijn; Anita Macdonald; Francjan J. Van Spronsen; Eddy A. Van Der Zee. Sleep Disturbances in Phenylketonuria: An Explorative Study in Men and Mice. Frontiers in Neurology 2017, 8, 167 .

AMA Style

Vibeke M. Bruinenberg, Marijke C. M. Gordijn, Anita Macdonald, Francjan J. Van Spronsen, Eddy A. Van Der Zee. Sleep Disturbances in Phenylketonuria: An Explorative Study in Men and Mice. Frontiers in Neurology. 2017; 8 ():167.

Chicago/Turabian Style

Vibeke M. Bruinenberg; Marijke C. M. Gordijn; Anita Macdonald; Francjan J. Van Spronsen; Eddy A. Van Der Zee. 2017. "Sleep Disturbances in Phenylketonuria: An Explorative Study in Men and Mice." Frontiers in Neurology 8, no. : 167.

Original research article
Published: 20 December 2016 in Frontiers in Behavioral Neuroscience
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To unravel the role of gene mutations in the healthy and the diseased state, countless studies have tried to link genotype with phenotype. However, over the years, it became clear that the strain of mice can influence these results. Nevertheless, identical gene mutations in different strains are often still considered equals. An example of this, is the research done in phenylketonuria (PKU), an inheritable metabolic disorder. In this field, a PKU mouse model (either on a BTBR or C57Bl/6 background) is often used to examine underlying mechanisms of the disease and/or new treatment strategies. Both strains have a point mutation in the gene coding for the enzyme phenylalanine hydroxylase which causes toxic concentrations of the amino acid phenylalanine in blood and brain, as found in PKU patients. Although the mutation is identical and therefore assumed to equally affect physiology and behavior in both strains, no studies directly compared the two genetic backgrounds to test this assumption. Therefore, this study compared the BTBR and C57Bl/6 wild-type and PKU mice on PKU-relevant amino acid- and neurotransmitter levels and at a behavioral level. The behavioral paradigms were selected from previous literature on the PKU mouse model and address four domains, namely 1) activity levels, 2) motor performance, 3) anxiety and/or depression-like behavior, and 4) learning and memory. The results of this study showed comparable biochemical changes in phenylalanine and neurotransmitter concentrations. In contrast, clear differences in behavioral outcome between the strains in all four above-mentioned domains were found, most notably in the learning and memory domain. The outcome in this domain seem to be primarily due to factors inherent to the genetic background of the mouse and much less by differences in PKU-specific biochemical parameters in blood and brain. The difference in behavioral outcome between PKU of both strains emphasizes that the consequence of the PAH mutation is influenced by other factors than Phe levels alone. Therefore, future research should consider these differences when choosing one of the genetic strains to investigate the pathophysiological mechanism underlying PKU-related behavior, especially when combined with new treatment strategies.

ACS Style

Vibeke M. Bruinenberg; Els Van Der Goot; Danique Van Vliet; Martijn J. De Groot; Priscila N. Mazzola; M. Rebecca Heiner-Fokkema; Martijn Van Faassen; Francjan J. Van Spronsen; Eddy A. Van Der Zee. The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background. Frontiers in Behavioral Neuroscience 2016, 10, 1 .

AMA Style

Vibeke M. Bruinenberg, Els Van Der Goot, Danique Van Vliet, Martijn J. De Groot, Priscila N. Mazzola, M. Rebecca Heiner-Fokkema, Martijn Van Faassen, Francjan J. Van Spronsen, Eddy A. Van Der Zee. The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background. Frontiers in Behavioral Neuroscience. 2016; 10 ():1.

Chicago/Turabian Style

Vibeke M. Bruinenberg; Els Van Der Goot; Danique Van Vliet; Martijn J. De Groot; Priscila N. Mazzola; M. Rebecca Heiner-Fokkema; Martijn Van Faassen; Francjan J. Van Spronsen; Eddy A. Van Der Zee. 2016. "The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background." Frontiers in Behavioral Neuroscience 10, no. : 1.

Brief report
Published: 26 March 2016 in Nutrients
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The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice.

ACS Style

Vibeke M. Bruinenberg; Danique Van Vliet; Amos Attali; Martijn C. De Wilde; Mirjam Kuhn; Francjan J. Van Spronsen; Eddy A. Van Der Zee. A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria. Nutrients 2016, 8, 185 .

AMA Style

Vibeke M. Bruinenberg, Danique Van Vliet, Amos Attali, Martijn C. De Wilde, Mirjam Kuhn, Francjan J. Van Spronsen, Eddy A. Van Der Zee. A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria. Nutrients. 2016; 8 (4):185.

Chicago/Turabian Style

Vibeke M. Bruinenberg; Danique Van Vliet; Amos Attali; Martijn C. De Wilde; Mirjam Kuhn; Francjan J. Van Spronsen; Eddy A. Van Der Zee. 2016. "A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria." Nutrients 8, no. 4: 185.

Original research article
Published: 19 January 2016 in Frontiers in Behavioral Neuroscience
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Introduction: with time-place learning (TPL), animals link an event with the spatial location and the time of day. The what-where-when TPL components make the task putatively episodic-like in nature. Animals use an internal sense of time to master TPL, which is circadian system based. Finding indications for a role of the hippocampus and (early) aging-sensitivity in TPL would strengthen the episodic-like memory nature of the paradigm. Methods: previously, we used C57Bl/6 mice for our TPL research. Here, we used CD1 mice which are less hippocampal-driven and age faster compared to C57Bl/6 mice. To demonstrate the low degree of hippocampal-driven performance in CD1 mice, a cross maze was used. The spontaneous alternation test was used to score spatial working memory in CD1 mice at four different age categories (young (3-6 months), middle-aged (7-11 months), aged (12-18 months) and old (>19 months)). TPL performance of middle-aged and aged CD1 mice was tested in a setup with either two or three time points per day (2-arm or 3-arm TPL task). Immunostainings was applied on brains of young and middle-aged C57Bl/6 mice that had successfully mastered the 3-arm TPL task. Results: in contrast to C57Bl/6 mice, middle-aged and aged CD1 mice were less hippocampus-driven and failed to master the 3-arm TPL task. They could, however, master the 2-arm TPL task primarily via an ordinal (non-circadian) timing system. c-Fos, CRY2, vasopressin (AVP), and pCREB were investigated. We found no differences at the level of the suprachiasmatic nucleus (SCN; circadian master clock), whereas CRY2 expression was increased in the hippocampal dentate gyrus. The most pronounced difference between TPL trained and control mice was found in c-Fos expression in the paraventricular thalamic nucleus, a circadian system relay station. Conclusions: These results further indicate a key role of CRY proteins in TPL and confirm the limited role of the SCN in TPL. Based on the poor TPL performance of CD1 mice, the results suggest age-sensitivity and hippocampal involvement in TPL. We suspect that TPL reflects an episodic-like memory task, but due to its functional nature, also entail the translation of experienced episodes into semantic rules acquired by training.

ACS Style

C. K. Mulder; M. P. Gerkema; E. A. Van Der Zee. Role of Aging and Hippocampus in Time-Place Learning: Link to Episodic-Like Memory? Frontiers in Behavioral Neuroscience 2016, 9, 362 .

AMA Style

C. K. Mulder, M. P. Gerkema, E. A. Van Der Zee. Role of Aging and Hippocampus in Time-Place Learning: Link to Episodic-Like Memory? Frontiers in Behavioral Neuroscience. 2016; 9 ():362.

Chicago/Turabian Style

C. K. Mulder; M. P. Gerkema; E. A. Van Der Zee. 2016. "Role of Aging and Hippocampus in Time-Place Learning: Link to Episodic-Like Memory?" Frontiers in Behavioral Neuroscience 9, no. : 362.

Review
Published: 01 March 2015 in Neuroscience & Biobehavioral Reviews
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Synapses are the building blocks of neuronal networks. Spines, the postsynaptic elements, are morphologically the most plastic part of the synapse. It is thought that spine plasticity underlies learning and memory processes, driven by kinases and cytoskeleton protein reorganization. Spine strength depends primarily on the number of incorporated glutamatergic receptors, which are more numerous in larger spines. Intrinsic and circadian fluctuations, occurring independently of presynaptic stimulation, demonstrate the native instability of spines. Despite innate spine instability some spines remain intact lifelong. Threats to spine survival are reduced by physical and mental activity, and declining sensory input, conditions characteristic for aging. Large spines are considered less vulnerable than thin spines, and in the older brain large spines are more abundant, whereas the thin spines are functionally weaker. It can be speculated that this shift towards memory spines contributes to enhanced retention of remote memories typically seen in the elderly. Gaining further insight in spine plasticity regulation, its homeostatic nature and how to maintain spine health will be important future research topics in Neuroscience

ACS Style

Eddy A. van der Zee. Synapses, spines and kinases in mammalian learning and memory, and the impact of aging. Neuroscience & Biobehavioral Reviews 2015, 50, 77 -85.

AMA Style

Eddy A. van der Zee. Synapses, spines and kinases in mammalian learning and memory, and the impact of aging. Neuroscience & Biobehavioral Reviews. 2015; 50 ():77-85.

Chicago/Turabian Style

Eddy A. van der Zee. 2015. "Synapses, spines and kinases in mammalian learning and memory, and the impact of aging." Neuroscience & Biobehavioral Reviews 50, no. : 77-85.

Journal article
Published: 01 February 2015 in Neurobiology of Learning and Memory
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Research indicates that neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD) in older patients. However, studies have mainly focused on hippocampal neuroinflammation and hippocampal-dependent learning and memory, which does not cover the whole spectrum of POCD. We hypothesized that regional differences in postoperative neuroinflammation in the brain may underlie variation in postoperative cognitive impairment. We aimed to investigate this hypothesis in a rat-model for POCD, by analyzing postoperative impairment in behavioral task performance and microglial activation in related brain areas. We subjected 25 months old Wistar rats to surgery and assessed spatial learning and memory, object and location recognition, reversal learning and exploratory behavior in the second postoperative week. The number and morphology of microglia were analyzed in the hippocampus, prefrontal cortex, striatum and amygdala on postoperative day 14. Control groups consisted of 3 and 25 months old rats that did not undergo surgery. We observed age related impairment in learning, memory and behavior, which was aggravated following surgery. Additionally, in old rats surgery was associated with signs of classical microglial activation in brain areas related to the impaired cognitive functions. These outcomes suggest that indeed neuroinflammation may be involved in POCD. Moreover, effects of age and surgery on cognition and microglial morphology seem to be area specific and hence cannot be generalized to the whole brain. This underpins the importance for expanding the research of POCD beyond the hippocampus.

ACS Style

Iris B. Hovens; Barbara L. van Leeuwen; Csaba Nyakas; Erik Heineman; Eddy A. van der Zee; Regien G. Schoemaker. Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiology of Learning and Memory 2015, 118, 74 -79.

AMA Style

Iris B. Hovens, Barbara L. van Leeuwen, Csaba Nyakas, Erik Heineman, Eddy A. van der Zee, Regien G. Schoemaker. Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiology of Learning and Memory. 2015; 118 ():74-79.

Chicago/Turabian Style

Iris B. Hovens; Barbara L. van Leeuwen; Csaba Nyakas; Erik Heineman; Eddy A. van der Zee; Regien G. Schoemaker. 2015. "Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats." Neurobiology of Learning and Memory 118, no. : 74-79.

Case reports
Published: 17 July 2014 in ADHD Attention Deficit and Hyperactivity Disorders
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Adult attention deficit hyperactivity disorder (ADHD) is associated with a variety of cognitive impairments, which were shown to affect academic achievement and quality of life. Current treatment strategies, such as stimulant drug treatment, were demonstrated to effectively improve cognitive functions of patients with ADHD. However, most treatment strategies are associated with a number of disadvantages in a considerable proportion of patients, such as unsatisfactory effects, adverse clinical side effects or high financial costs. In order to address limitations of current treatment strategies, whole-body vibration (WBV) might represent a novel approach to treat cognitive dysfunctions of patients with ADHD. WBV refers to the exposure of the whole body of an individual to vibration and was found to affect physiology and cognition. In the present study, WBV was applied on 10 consecutive days to an adult diagnosed with ADHD. Neuropsychological assessments were performed repeatedly at three different times, i.e., the day before the start of the treatment, on the day following completion of treatment and 14 days after the treatment have been completed (follow-up). An improved neuropsychological test performance following WBV treatment points to the high clinical value of WBV in treating patients with neuropsychological impairments such as ADHD.

ACS Style

Anselm B. M. Fuermaier; Lara Tucha; Janneke Koerts; Meinris Van Den Bos; G. Ruben H. Regterschot; Edzard B. Zeinstra; Marieke J. G. Van Heuvelen; Eddy A. Van Der Zee; Klaus W. Lange; Oliver Tucha. Whole-body vibration improves cognitive functions of an adult with ADHD. ADHD Attention Deficit and Hyperactivity Disorders 2014, 6, 211 -220.

AMA Style

Anselm B. M. Fuermaier, Lara Tucha, Janneke Koerts, Meinris Van Den Bos, G. Ruben H. Regterschot, Edzard B. Zeinstra, Marieke J. G. Van Heuvelen, Eddy A. Van Der Zee, Klaus W. Lange, Oliver Tucha. Whole-body vibration improves cognitive functions of an adult with ADHD. ADHD Attention Deficit and Hyperactivity Disorders. 2014; 6 (3):211-220.

Chicago/Turabian Style

Anselm B. M. Fuermaier; Lara Tucha; Janneke Koerts; Meinris Van Den Bos; G. Ruben H. Regterschot; Edzard B. Zeinstra; Marieke J. G. Van Heuvelen; Eddy A. Van Der Zee; Klaus W. Lange; Oliver Tucha. 2014. "Whole-body vibration improves cognitive functions of an adult with ADHD." ADHD Attention Deficit and Hyperactivity Disorders 6, no. 3: 211-220.

Journal article
Published: 01 May 2014 in Brain, Behavior, and Immunity
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Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway. To study the time course of post-surgical (neuro)inflammation, changes in the BDNF-pathway and POCD, we subjected 3 months old male Wistar rats to abdominal surgery and implanted a jugular vein catheter for timed blood sampling. Cognition, affective behavior and markers for (neuro)inflammation. BDNF and neurogenesis were assessed at 1, 2 and 3 weeks following surgery. Rats displayed changes in exploratory activity shortly after surgery, associated with postoperatively elevated IL-6 plasma levels. Spatial learning and memory were temporarily impaired in the first 2 weeks following surgery, whereas non-spatial cognitive functions seemed unaffected. Analysis of brain tissue revealed increased neuroinflammation (IL-1B and microgliosis) 7 days following surgery, decreased BDNF levels on postoperative day 14 and 21, and decreased neurogenesis until at least 21 days following surgery. These findings indicate that in young adult rats only spatial learning and memory is affected by surgery, suggesting hippocampal dependent cognition is especially vulnerable to surgery-induced impairment. The observed differences in time course following surgery and relation to plasma IL-6 suggest cognitive dysfunction and mood changes comprise distinct features of postoperative behavioral impairment. The postoperative changes in neuroinflammation, BDNF and neurogenesis may represent aspects of the underlying mechanism for POCD. Future research should be aimed to elucidate how these players interact. (C) 2014 Elsevier Inc. All rights reserved

ACS Style

Iris B. Hovens; Regien G. Schoemaker; Eddy A. van der Zee; Anthony Absalom; Erik Heineman; Barbara van Leeuwen. Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning. Brain, Behavior, and Immunity 2014, 38, 202 -210.

AMA Style

Iris B. Hovens, Regien G. Schoemaker, Eddy A. van der Zee, Anthony Absalom, Erik Heineman, Barbara van Leeuwen. Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning. Brain, Behavior, and Immunity. 2014; 38 ():202-210.

Chicago/Turabian Style

Iris B. Hovens; Regien G. Schoemaker; Eddy A. van der Zee; Anthony Absalom; Erik Heineman; Barbara van Leeuwen. 2014. "Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning." Brain, Behavior, and Immunity 38, no. : 202-210.