Neuroscience
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Despite advances in surgery, patients with nerve injuries frequently have functional deficits. We previously demonstrated in a rat model that daily electrical muscle stimulation (EMS) following peripheral nerve injury and repair enhances reinnervation, detectable as early as two weeks post-injury. In this study, we explain the enhanced early reinnervation observed with electrical stimulation. ⋯ The corresponding levels of trophic factor mRNA within the distal stump were not different from one another, indicating that the intramuscular electrical stimulus does not modulate Schwann cell-derived trophic factor transcription. Stimulation over a three-month period maintained elevated muscle-derived GDNF but not BDNF mRNA. In conclusion, EMS elevates intramuscular trophic factor mRNA levels which may explain how EMS enhances neural regeneration following nerve injury.
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Traumatic brain injury (TBI) is a major cause of morbidity and mortality world-wide and can result in persistent cognitive, sensory and behavioral dysfunction. Understanding the time course of TBI-induced pathology is essential to effective treatment outcomes. We induced TBI in rats using an impact acceleration method and tested for sensorimotor skill and sensory sensitivity behaviors for two weeks to find persistently poor outcomes post-injury. ⋯ Further, there were abnormalities in temporal response patterns such that in layers 3-5 there was a temporal broadening of response patterns in response to both whisker deflection stimulus types and in L2 a narrowing of temporal patterns in response to the complex stimulus. Thus, at two weeks post-TBI, supragranular hypo-excitation has evolved to include deep cortical layers likely as a function of progressive atrophy and neurodegeneration. These results are consistent with the hypothesis that TBI alters the delicate excitatory/inhibitory balance in cortex and likely contributes to temporal broadening of responses and restricts the ability to code for complex sensory stimuli.
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Anticholinergic medications can exert their effects by acting on muscarinic receptors, which mediates the function of acetylcholine in the central nervous system. Acetylcholine plays a number of roles, particularly in regard to the control of muscle activity and normal cognitive functioning. Eighteen subjects were recruited into the human, double-blind, placebo-controlled, four-way crossover study. ⋯ Promethazine was the only medication to influence the modified attention network test (ANT) by increasing the conflict effect and grand mean reaction time (RT). Pupil diameter and blink rate were both influenced by the central anticholinergics during performance of the cognitive test, thus highlighting the importance of central cholinergic pathways in the control of pupil diameter and blink rate. The collective effects of central anticholinergics on the modified ANT and on pupil diameter and blink rate during its performance, conveys the importance of central cholinergic pathways in cognitive function.
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Mitochondrial changes and oxidative stress in a mouse model of Zellweger syndrome neuropathogenesis.
Zellweger syndrome (ZS) is a peroxisome biogenesis disorder that involves significant neuropathology, the molecular basis of which is still poorly understood. Using a mouse model of ZS with brain-restricted deficiency of the peroxisome biogenesis protein PEX13, we demonstrated an expanded and morphologically modified brain mitochondrial population. ⋯ Similar overall changes were observed for glial cells. In toto, these findings suggest that mitochondrial oxidative stress and aberrant mitochondrial dynamics are associated with the neuropathology arising from PEX13 deficiency.
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Anxiety disorders are more likely to occur in women than in men, usually emerge during adolescence and exhibit high comorbidity with alcohol use disorders (AUD). Adolescents with high levels of anxiety or heightened reactivity to stress may be at-risk for developing AUD. An approach to analyze if high levels of inborn anxiety predict greater ethanol drinking is to assess the latter variable in subjects classified as high- or low-anxiety responders. ⋯ Stress induced a significant increase in FOS immunoreactivity at the paraventricular nucleus, yet this effect was unaffected by level of anxiety response. Female adolescents with high levels of basal anxiety may be at-risk for exhibiting increased predisposition for ethanol intake and preference. The study also indicates that stress may exert differential effects on adolescent ethanol intake as a function of the level of anxiety response.