Neuroscience
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In rodents, chronic intermittent ethanol vapor exposure (CIE) produces alcohol dependence, alters the structure and activity of pyramidal neurons and decreases the number of oligodendroglial progenitors in the medial prefrontal cortex (mPFC). In this study, adult Wistar rats were exposed to seven weeks of CIE and were withdrawn from CIE for 21 days (protracted abstinence; PA). Tissue enriched in the mPFC was processed for Western blot analysis and Golgi-Cox staining to investigate the long-lasting effects of CIE on the structure of mPFC neurons and the levels of myelin-associated proteins. ⋯ PA produced hypophosphorylation of the GR at Ser-232 without affecting expression of total protein. These findings demonstrate persistent and compensatory effects of ethanol in the mPFC long after cessation of CIE, including enhanced myelin production and impaired GR function. Collectively, these results suggest a novel relationship between oligodendrocytes and GR in the mPFC, in which stress may alter frontal cortex function in alcohol dependent subjects by promoting hypermyelination, thereby altering the cellular composition and white matter structure in the mPFC.
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Transactive response DNA-binding protein 43 (TDP-43) is a predominantly nuclear, ubiquitously expressed RNA and DNA-binding protein. It recognizes and binds to UG repeats and is involved in pre-mRNA splicing, mRNA stability and microRNA metabolism. TDP-43 is essential in early embryonic development but accumulates in cytoplasmic aggregates in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal lobar degeneration (FTLD). ⋯ We show that Ran-binding protein 1 (RanBP1), DNA methyltransferase 3 alpha (Dnmt3a) and chromogranin B (CgB) are downregulated upon TDP-43 knockdown. Subsequently, transportin 1 level is increased as a result of RanBP1 depletion. Improper regulation of these proteins and the subsequent disruption of cellular processes may play a role in the pathogenesis of the TDP-43 proteinopathies ALS and FTLD.
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To measure changes in amplitudes of vestibular evoked myogenic potentials (VEMPs) elicited from neck, upper and lower limb muscles during a quiet standing task with increased postural threat achieved by manipulating surface height. ⋯ Postural threat significantly increased vestibulospinal reflex (VSR) gains. Results demonstrate that VEMPs can be used to test different VSR pathways simultaneously during stance. Since fear and anxiety are prevalent with vestibular disorders, they should be considered as potential contributing factors for clinical vestibular outcome measures.
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Motor commands issued by the CNS are based upon memories of past experiences with similar objects, the current state of the hand and arm postures, and sensory input. Thus widespread somatosensory information is available to form precise representations of hand shape on which to base motor commands to match a desired posture or movement. The aim of this study was to examine the extent to which somatosensory information reflecting external influences on independent finger movement is incorporated into the perception of hand shape driving the motor command. ⋯ The hypothesis was that the same synergies (patterns of activation across muscles) would be used to complete the task but would be rescaled with respect to condition. The results demonstrated that rescaling the patterns of multi-muscle activity from the unconstrained condition could not equivalently represent those from the constrained conditions. Thus it appears that external restriction of independent finger movement was signaled by somatosensory feedback and incorporated into the desired state driving the motor command resulting in selective activation of groups of muscles.
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The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on-2 days off; P25-P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). ⋯ Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood.