Chondroitin sulphate proteoglycans in the extracellular matrix restrict plasticity in the adult central nervous system and their digestion with chondroitinase reactivates plasticity. However the structures in the extracellular matrix that restrict plasticity are unknown. There are many changes in the extracellular matrix as critical periods for plasticity close, including changes in chondroitin sulphate proteoglycan core protein levels, changes in glycosaminoglycan sulphation and the appearance of dense chondroitin sulphate proteoglycan-containing perineuronal nets around many neurons. We show that formation of perineuronal nets is triggered by neuronal production of cartilage link protein Crtl1 (Hapln1), which is up-regulated in the visual cortex as perineuronal nets form during development and after dark rearing. Mice lacking Crtl1 have attenuated perineuronal nets, but the overall levels of chondroitin sulphate proteoglycans and their pattern of glycan sulphation are unchanged. Crtl1 knockout animals retain juvenile levels of ocular dominance plasticity and their visual acuity remains sensitive to visual deprivation. In the sensory pathway, axons in knockout animals but not controls sprout into the party denervated cuneate nucleus. The organization of chondroitin sulphate proteoglycan into perineuronal nets is therefore the key event in the control of central nervous system plasticity by the extracellular matrix.

Health care professionals (HCPs) are a population at risk for high levels of burnout and compassion fatigue. The aim of the present systematic review was to give an overview on recent literature about mindfulness and compassion characteristics of HCPs, while exploring the effectiveness of techniques, involving the two aspects, such as MBSR or mindfulness intervention and compassion fatigue-related programs. A search of databases, including PubMed and PsycINFO, was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and the methodological quality for this systematic review was appraised using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews-2). The number of articles that met the inclusion criteria was 58 (4 RCTs, 24 studies with pre-post measurements, 12 cross-sectional studies, 11 cohort studies and 7 qualitative studies). MBSR intervention was effective at improving, and maintaining, mindfulness and self-compassion levels and to improve burnout, depression, anxiety, stress. The most frequently employed interventional strategies were mindfulness-related trainings that were effective at improving mindfulness and self-compassion, but not compassion fatigue, levels. Compassion-related interventions have been shown to improve self-compassion, mindfulness and interpersonal conflict levels. Mindfulness was effective at improving negative affect and compassion fatigue, while compassion satisfaction may be related to cultivation of positive affect. This systematic review summarized the evidence regarding mindfulness- and compassion-related qualities of HCPs as well as potential effects of MBSR, mindfulness-related and compassion-related interventions on professionals' psychological variables like mindfulness, self-compassion and quality of life. Combining structured mindfulness and compassion cultivation trainings may enhance the effects of interventions, limit the variability of intervention protocols and improve data comparability of future research.

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.

A decrease in brain-derived neurotrophic factor (BDNF), a neurotrophin essential for synaptic function, plasticity and neuronal survival, is evident early in the progression of Alzheimer’s disease (AD), being apparent in subjects with mild cognitive impairment or mild AD, and both proBDNF and mature BDNF levels are positively correlated with cognitive measures. BDNF delivery is, therefore, considered of great interest as a potentially useful therapeutic strategy to contrast AD. Invasive BDNF administration has indeed been recently used in animal models of AD with promising results in rescuing memory deficits, synaptic density and cell loss. Here, we tested whether non-invasive intranasal administration of different BDNF concentrations after the onset of cognitive and anatomical deficits (6 months of age) could rescue neuropathological and memory deficits in AD11 mice, a model of NGF deprivation-induced neurodegeneration. In addition to AD hallmarks, we investigated BDNF effects on microglia presence in the brain of AD11 mice, since alterations in microglia activation have been associated with ageing-related cognitive decline and with the progression of neurodegenerative diseases, including AD. We found that intranasal delivery of 42 pmol BDNF (1 μM), but not PBS, was sufficient to completely rescue performance of AD11 mice both in the object recognition test and in the object context test. No further improvement was obtained with 420 pmol (10 μM) BDNF dose. The strong improvement in memory performance in BDNF-treated mice was not accompanied by an amelioration of AD-like pathology, Aβ burden, tau hyperphosphorylation and cholinergic deficit, but there was a dramatic decrease of CD11b immunoreactive brain microglia. These results reinforce the potential therapeutic uses of BDNF in AD and the non-invasive intranasal route as an effective delivery strategy of BDNF to the brain. They also strengthen the connection between neuroinflammation and neurodegenerative dementia and suggest microglia as a possible mediator of BDNF therapeutic actions in the brain.

Research on the neuroscience of fear in both humans and non-humans has suggested that a lack of acquisition of safety cues might be a biological hallmark of posttraumatic stress disorder (PTSD). Danger perception, and in particular, feeling as one's own life is in danger, is thought to represent a major predictor of PTSD. Persistent danger perception is concurrently associated with a persistence of lack of safety. However, despite several research efforts, no validated psychometric tools exist regarding psychological safety as a unique core construct in the domain of a soothing-contentment system. By including social, compassionate, and bodily components, the Neuroception of Psychological Safety Scale (NPSS), neurophysiologically rooted in the polyvagal theory, aims to specifically assess psychological safety. Originally developed in English, we employed a rather large non clinical sample to validate our Italian translation of the NPSS (n = 338) and the scale was found to retain a three-factor structure. In light of its positive moderate correlations with the Unconditional Self-Kindness Scale (ρ = 0.376) and the Self-Compassion Scale-Short-Form (ρ = 0.481), good convergent validity and robust psychometric properties were shown by the NPSS. The Subjective Traumatic Outlook Questionnaire (ρ = −0.283) and the three subscales of the Body Perception Questionnaire-22—Body Awareness (ρ = −0.103), Supradiaphragmatic Reactivity (ρ = −0.234), and Body Awareness/Subdiaphragmatic Reactivity (ρ = −0.146)—were found to have weak negative correlations with the NPSS, which further demonstrated its good discriminant validity. Eventually, the NPSS was found to show good test-retest reliability (intraclass correlation coefficient = 0.922; three-week time interval), and its usage is fostered in clinical and research contexts where the evaluation of psychological safety is of relevance.