Neuroscience
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Stress is an adaptive and coordinated response to endogenous or exogenous stressors that pose an unpleasant and aversive threat to an individual's homeostasis and wellbeing. Glucocorticoids, corticosterone (CORT) in rodents and cortisol in humans, are adrenal steroids which are released in response to stressful stimuli. Although they help individuals to cope with stress, their overexposure in animals has been implicated in hippocampal dysfunction and neuronal loss. ⋯ OT was unable to protect primary hippocampal neurons prepared from OTR KO mice from CORT-induced apoptosis. These results indicate that OT has inhibitory effects on CORT-induced neuronal death in primary hippocampal neurons via acting on OTR. The findings suggest a therapeutic potential of OT in the treatment of stress-related disorders.
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Parkinson's disease (PD) related to homozygous mutations in the Pink1 gene is associated with nigrostriatal dopamine depletion and a wide range of sensorimotor deficits. In humans and animal models of PD, not all sensorimotor deficits are levodopa-responsive. We hypothesized that the underlying mechanisms of locomotion, limb control, and vocal communication behavior include other pathologies. ⋯ Pearson's correlations showed that increases in time to traverse a tapered balance beam are significantly associated with reductions in striatal dopamine. Ultrasonic vocalization complexity was positively correlated with LC norepinephrine concentrations. These data support the evolving hypothesis that differences in neural substrates and early-onset noradrenergic mechanisms in the brainstem may contribute to pathogenesis in the Pink1 -/- rat.
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It has been shown that brain-injured patients (BIP) have exacerbated mirror movements (MM). MM are involuntary contractions occurring in homologous muscles contralateral to voluntary movements, particularly in distal upper limb muscles. Attentional and inhibitory processes have been proposed as key factors to explain the level of MM. ⋯ Moreover, (3) in all participants - independent of the type of task used to evaluate MM - the amount and intensity of MM was predicted by the level of executive control, assessed by the Trail Making Test. High level of MM was associated with weak executive control abilities. This study is the first to highlight the link between MM and executive functioning, which may have implications for rehabilitation in BIP.
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Emerging evidence indicates that transcriptome alterations due to epigenetic deregulation concur to ALS pathogenesis. Accordingly, pan-histone deacetylase (HDAC) inhibitors delay ALS development in mice, but these compounds failed when tested in ALS patients. Possibly, lack of selectivity toward specific classes of HDACs weakens the therapeutic effects of pan-HDAC inhibitors. ⋯ Conversely, increase in specific Class II HDACs (-4, -5 and -6) occurs in skeletal muscle of mice with severe neuromuscular impairment. Importantly, treatment with MC1568 causes early improvement of motor performances that vanishes at later stages of disease. Notably, motor improvement is not paralleled by reduced motor neuron degeneration but by increased skeletal muscle electrical potentials, reduced activation of mir206/FGFBP1-dependent muscle reinnervation signaling, and increased muscle expression of myogenic genes.
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In the primary visual cortex (V1), neuronal responses to stimuli within the receptive field (RF) are modulated by stimuli in the RF surround. A common effect of surround modulation is surround suppression, which is dependent on the feature difference between stimuli within and surround the RF and is suggested to be involved in the perceptual phenomenon of figure-ground segregation. In this study, we examined the relationship between feature-specific surround suppression of V1 neurons and figure detection behavior based on figure-ground feature difference. ⋯ Consistent with the behavioral performance, the sensitivity of V1 neurons to RF-surround phase difference could be influenced by stimulus contrast. Furthermore, inhibiting V1 by optogenetically activating either parvalbumin (PV)- or somatostatin (SOM)-expressing inhibitory neurons both decreased the behavioral performance of figure detection. Thus, the phase-specific surround suppression in V1 represents a neural correlate of figure detection behavior based on figure-ground phase discontinuity.