Neuroscience
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Impaired balance may limit mobility and daily activities, and plays a key role in the elderly falling. Maintaining balance requires a concerted action of the sensory, nervous and motor systems, whereby cause and effect mutually affect each other within a closed loop. Aforementioned systems and their connecting pathways are prone to chronological age and disease-related deterioration. ⋯ This paper outlines the multiple deteriorations of the underlying systems that may be involved in standing balance, which have to be detected early to prevent impaired standing balance. An overview of clinically used balance tests shows that early detection of impaired standing balance and identification of causal mechanisms is difficult with current tests, thereby hindering the development of well-timed and target-oriented interventions as described next. Finally, a new approach to assess standing balance and to detect the underlying deteriorations is proposed.
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Although extensively investigated in socio-cognitive neuroscience, empathy is difficult to study. The first difficulty originates in its multifaceted nature. According to the multidimensional model, empathy combines emotional, automatic (simulation), cognitive (mentalizing) and regulatory (executive functions) processes. ⋯ However, at 333-424ms, empathy triggered greater co-activations in the right IFG and dorsolateral prefrontal cortex (dlPFC) (executive functions). Linking together our present and prior (Thirioux et al., 2010) findings from the same dataset, we suggest that this greater recruitment of the right dlPFC monitors the shift from egocentered and first-person-like mechanisms in the MNS to heterocentered and second-person-like mechanisms in the left temporo-parietal junction within the MENT, i.e., reflecting the onset of perspective-change processes in the neural time course of empathy. Contrasting with sympathy, this recruitment of the executive functions could modulate the output end of the mirroring processing in the premotor and sensorimotor cortices.
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Neuropathologic processes such as cerebral ischemia can enhance neurogenesis. Angiopoietin-1 (Ang1) emerges as a critical regulator of physiological and pathological angiogenesis during embryonic and postnatal life. Although Ang1 could protect peripheral vasculature from vascular leakage following ischemic injury, the role of Ang1 in long-term neurological recovery after ischemic stroke remains elusive. ⋯ Our results demonstrated that lentivirus-mediated Ang1 gene transfer led to improved neurological behavior and reduced infarction volume, and protected against blood-brain barrier (BBB) leakage in the ischemic rats. In addition, we revealed that these effects of Ang1 are related to the ability of Ang1 to increase vascular density and accelerate endogenous neuronal differentiation. These findings suggest that Ang1 is a promising agent for the treatment of cerebral ischemia.
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Dimebon (dimebolin or latrepirdine), originally developed as an anti-histaminic drug, has been investigated and proposed as a cognitive enhancer for treating neurodegenerative disorders such as Alzheimer's and Huntington's diseases, and more recently schizophrenia. This study was conducted to evaluate the potential neuroprotective effect of dimebon during brain ischemia using rat hippocampal slices subjected to oxygen and glucose deprivation followed by a reoxygenation period (OGD/Reox) or glutamate excitotoxicity. Dimebon, incubated during the OGD/Reox period, caused a concentration -dependent protective effect of hippocampal slices; maximum protection (85%) was achieved at 30μM. ⋯ In the glutamate-induced excitotoxicity model, dimebon also afforded a concentration-dependent protective effect that was significantly higher than that obtained with memantine, a non-competitive N-methyl-d-aspartate (NMDA) antagonist. When changes in the intracellular calcium concentration were evaluated in Fluo-4-loaded rat hippocampal neurons, glutamate-induced calcium transients were reduced by 20% with dimebon. These results suggest that dimebon could counteract different pathophysiological processes during ischemic brain damage and, could therefore, be considered as a novel therapeutic strategy for cerebral ischemia-reoxygenation injury.
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Respiratory disturbances are a primary phenotype of the neurological disorder, Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Mouse models generated with null mutations in Mecp2 mimic respiratory abnormalities in RTT girls. Large deletions, however, are seen in only ∼10% of affected human individuals. ⋯ We found that both Mecp2(T158A/+) and Mecp2(R168X/+) heterozygotes display augmented hypoxic ventilatory responses and depressed hypercapnic responses, compared to wild-type controls. Interestingly, the incidence of apnea was much greater in Mecp2(R168X/+) heterozygotes, 189 per hour, than Mecp2(T158A/+) heterozygotes, 41 per hour. These results demonstrate that different RTT mutations lead to distinct respiratory phenotypes, suggesting that characterization of the respiratory phenotype may reveal functional differences between MeCP2 mutations and provide insights into the pathophysiology of RTT.