The dominant hypothesis about the pathogenesis of Alzheimer’s disease (AD) is the “amyloid cascade” concept and modulating the expression of proteins involved in the metabolism of amyloid-beta (Aβ) is proposed as an effective strategy for the prevention and therapy of AD. Recently, we found that an antibiotic ceftriaxone (CEF), which possesses neuroprotective activity, reduced cognitive deficits and neurodegenerative changes in OXYS rats, a model of sporadic AD. The molecular mechanisms of this effect are not completely clear, we suggested that the drug might serve as the regulator of the expression of the genes involved in the metabolism of Aβ and the pathogenesis of AD. The study was aimed to determine the effects of CEF on mRNA levels of Bace1 (encoding β-secretase BACE1 involved in Aβ production), Mme, Ide, Ece1, Ace2 (encoding enzymes involved in Aβ degradation), Epo (encoding erythropoietin related to endothelial function and clearance of Aβ across the blood brain barrier) in the frontal cortex, hippocampus, striatum, hypothalamus, and amygdala of OXYS and Wistar (control strain) male rats. Starting from the age of 14 weeks, animals received CEF (100 mg/kg/day, i.p., 36 days) or saline. mRNA levels were evaluated with RT-qPCR method. Biochemical parameters of plasma were measured for control of system effects of the treatment. To better understand strain variations studied here, we compared the gene expression between untreated OXYS and Wistar rats. This comparison showed a significant decrease in mRNA levels of Ace2 in the frontal cortex and hypothalamus, and of Actb in the amygdala of untreated OXYS rats. Analysis of potential effects of CEF revealed its novel targets. In the compound-treated OXYS cohort, CEF diminished mRNA levels of Bace1 and Ace2 in the hypothalamus, and Aktb in the frontal cortex. Furthermore, CEF augmented Mme, Ide, and Epo mRNA levels in the amygdala as well as the levels of Ece1 and Aktb in the striatum. Finally, CEF also attenuated the activity of ALT and AST in plasma of OXYS rats. Those findings disclosed novel targets for CEF action that might be involved into neuroprotective mechanisms at early, pre-plaque stages of AD-like pathology development.

Background: Recent studies have demonstrated that the assessment of postural performance may be a potentially reliable and objective marker of the psychomotor retardation (PMR) in the major depressive disorder (MDD). One of the important facets of MDD-related PMR is reflected in disrupted central mechanisms of psychomotor control, heavily influenced by compelling maladaptive depressive rumination. In view of this we designed a research paradigm that included sequential execution of simple single-posture task followed by more challenging divided attention posture tasks, involving concurring motor and ideomotor workloads. Another difficulty dimension assumed executing of all the tasks with eyes open (EO) (easy) and closed (EC) (difficult) conditions. We aimed at investigating the interplay between the severity of MDD, depressive rumination, and efficiency of postural performance. Methods: Compared with 24 age- and body mass index-matched healthy controls (HCs), 26 patients with MDD sequentially executed three experimental tasks: (1) single-posture task of maintaining a quiet stance (ST), (2) actual posture-motor dual task (AMT); and (3) mental/imaginary posture-motor dual task (MMT). All the tasks were performed in the EO and the EC conditions. The primary dependent variable was the amount of kinetic energy (E) expended for the center of pressure deviations (CoPDs), whereas the absolute divided attention cost index showed energy cost to the dual-tasking vs. the single-posture task according to the formula: ΔE = (E_Dual-task -E_Single-task). Results: The signs of PMR in the MDD group were objectively indexed by deficient posture control in the EC condition along with overall slowness of fine motor and ideomotor activity. Another important and probably more challenging feature of the findings was that the posture deficit manifested in the ST condition was substantially and significantly attenuated in the MMT and AMT performance dual-tasking activity. A multiple linear regression analysis evidenced further that the dual-tasking energy cost (i.e., ΔE) significantly predicted clinical scores of severity of MDD and depressive rumination. Conclusion: The findings allow to suggest that execution of concurrent actual or imaginary fine motor task with closed visual input deallocates attentional resources from compelling maladaptive depressive rumination thereby attenuating severity of absolute dual-tasking energy costs for balance maintenance in patients with MDD. Significance: Quantitative assessment of PMR through measures of the postural performance in dual-tasking may be useful to capture the negative impact of past depressive episodes, optimize the personalized treatment selection, and improve the understanding of the pathophysiological mechanisms underlying MDD.

The aim of the study was to investigate whether visual stimuli have the same potency to increase electroencephalography (EEG) delta wave power density during non-rapid eye movement (NREM) sleep as do auditory stimuli that may be practical in the treatment of some sleep disturbances. Nine healthy subjects underwent two polysomnography sessions—adaptation and experimental—with EEG electrodes positioned at Fz–Cz. Individually adjusted auditory (pink noise) and visual (light-emitting diode (LED) red light) paired 50-ms signals were automatically presented via headphones/eye mask during NREM sleep, shortly (0.75–0.90 s) after the EEG wave descended below a preset amplitude threshold (closed-loop in-phase stimulation). The alternately repeated 30-s epochs with stimuli of a given modality (light, sound, or light and sound simultaneously) were preceded and followed by 30-s epochs without stimulation. The number of artifact-free 1.5-min cycles taken in the analysis was such that the cycles with stimuli of different modalities were matched by number of stimuli presented. Acoustic stimuli caused an increase (p < 0.01) of EEG power density in the frequency band 0.5–3.0 Hz (slow waves); the values reverted to baseline at post-stimuli epochs. Light stimuli did not influence EEG slow wave power density (p > 0.01) and did not add to the acoustic stimuli effects. Thus, dim red light presented in a closed-loop in-phase fashion did not influence EEG power density during nocturnal sleep.

Brain neurotrophic factor (BDNF) is one of the key indicators of neurogenesis and neuroplasticity. The concentration of BDNF in the blood is positioned as a potential biomarker of the development and dynamics of neuropsychiatric diseases. However, the extent to which its concentration in the blood reflects its content in the brain is not clear; a literature analysis on this matter has not been performed. This review provides basic information about the biological role, content and regulation of BDNF in the body (chapter I), about the concentration of BDNF in the blood in neuropsychiatric diseases (chapter II), and analyzes the correlation of BDNF content in the brain and blood (chapter III, the main one). In 5 out of 6 studies on intact animals identified as a result of the literature search, a statistically significant positive correlation between the concentration of BDNF in the brain and blood is reported. However, the correlation coefficient is variable and generally not high - from 0.40 to 0.83. There were no during-life studies performed in human. Some post-mortem studies have reported a significant association between BDNF indices values in the brain and in the periphery. Thus, the question of the extent to which BDNF in the blood is diagnostically valuable remains unanswered.