Neuroscience
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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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Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. ⋯ Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro, as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS.
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Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. ⋯ This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control.
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Cortices are non-uniform in their capacity for adaptive changes. In cat area 17, pinwheel centers of the orientation map demonstrated much greater selectivity shifts after the orientation adaptation than the iso-orientation domains (Dragoi et al., 2001a). However, whether this heterogeneity exists in other visual cortical regions remains unclear. ⋯ However, at either pinwheel centers or iso-orientation domains, the selectivity shifts in area 21a were all consistently greater than those in area 17, even though the heterogeneity in the orientation distribution was similar in the two areas. More importantly, in our short-term adaptation protocol, orientation adaptation in area 17 resulted in mostly repulsive shifts at the pinwheel center region, while in area 21a, it induced both repulsive and attractive effects. These results suggest that both common and distinct strategies exist for orientation adaptation across cortices and sub-regions.
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Comparative Study
Sex Differences and Estrous Cycle Changes in Synaptic Plasticity-related microRNA in the Rat Medial Amygdala.
The posterodorsal medial amygdala (MePD) is a sex steroid-sensitive and sexually dimorphic subcortical area that dynamically modulates social behaviors in rats. As different microRNA (miRNA) can act as post-transcriptional regulators of synaptic processing, we addressed changes that occur in miRNA expression in the MePD of males and females along the estrous cycle. The expression of miR25-3p, miR132-3p, miR138-5p, miR181a-5p, miR195-5p, and miR199a-5p, involved in neuronal cytoskeleton remodeling and synaptic plasticity, were evaluated by RT-qPCR. ⋯ In addition, diestrus females showed higher values of miR25-3p, miR181a-5p, and miR195-5p when compared to estrus females. These miRNA expression profiles indicate a variable and fine-tuned protein regulation in the adult MePD. It is likely that these miRNA can be involved in structural and functional synaptic features and plasticity characteristic of males and cycling females and for the MePD regulation of mammalian reproduction.