Neuroscience
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We examined the contribution of the sodium channel isoform Nav1.8 to retinal function using the specific blocker A803467. We found that A803467 has little influence on the electroretinographic (ERG) a- and b-waves, but significantly reduces the oscillatory potentials to 40-60% of their original amplitude, with significant changes in implicit time in the rod-driven range. To date, only two cell types were found in mouse to express Nav1.8; the starburst amacrine cells (SBAC), and a subtype of retinal ganglion cells (RGC). ⋯ We have previously shown that RGCs have only a minor contribution to the oscillatory potentials (Smith et al., 2014), therefore suggesting that starburst amacrine cells might be a significant contributor to this ERG component. Targeting SBACs with the cholinergic neurotoxin ethylcholine mustard aziridinium (AF64A) caused reduction in the amplitude of the OPs similar to A803467. Our results, both using the ERG and MEA recordings from retina ganglion cells, suggest that Nav1.8 plays a role in modulating specific aspects of the retinal physiology and that SBACs are a fundamental cellular contributor to the OPs in mice, a clear demonstration of the dichotomy between ERG b-wave and oscillatory potentials.
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Glutaryl-CoA dehydrogenase (GCDH) is a mitochondrial enzyme that is involved in the degradation of tryptophan, lysine and hydroxylysine. Deficient enzyme activity leads to glutaric aciduria type-I (GA-I). This neurometabolic disease usually manifests with acute encephalopathic crises and striatal neuronal death in early childhood leading to an irreversible dystonic-dyskinetic movement disorder. ⋯ GCDH was found widely expressed in embryonic and adult rat tissues. In rat embryos GCDH is predominantly expressed in brain implying an important role for brain development. Interestingly, GCDH was found to be significantly expressed in different other organs (e.g. kidney, gut) in adult rats probably explaining the evolving phenotype in GA-I patients.
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Hydrogen sulfide (H2S) is an endogenous gasotransmitter with neuroprotective properties that participates in the regulation of transmitter release and neuronal excitability in various brain structures. The role of H2S in the growth and maturation of neural networks however remains unclear. The aim of the present study is to reveal the effects of H2S on neuronal spontaneous activity relevant to neuronal maturation in hippocampal slices of neonatal rats. ⋯ The subsequent decrease in the neuronal activity by H2S appears to be due to the rightward shift of activation and inactivation of voltage-gated Na(+) currents, thus preventing network activity. NaHS also reduced NMDA-mediated currents, without essential effect on AMPA/kainate or GABAA-mediated currents Finally, H2S abolished the interictal-like events induced by bicuculline. In summary, our results suggest that through the inhibitory action on voltage-gated Na(+) channels and NMDA receptors, H2S prevents the enhanced neuronal excitability typical to early hippocampal networks.
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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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Although there is little overlap in core diagnostic criteria for ADHD and Autism Spectrum Disorder (ASD), ASD symptoms are estimated to co-occur in children with ADHD in 20-50% of cases. As motor control deficits are common to both disorders, we investigated the impact of ASD symptoms on ocular motor control in children with Attention Deficit Hyperactivity Disorder-Combined Type (ADHD-CT), using a cued saccade paradigm sensitive to cerebellar ocular motor impairment in ASD. ⋯ Our results revealed that saccade profiles of the ADHD-CT group showed a pattern of hypermetria and altered main sequence. As the cerebellum is crucially involved in the regulation of saccade parameters, we propose that this pattern of deficit in ADHD-CT is consistent with the widely reported morphological abnormalities in ocular motor vermis (cerebellar lobules VI-VII) in ADHD-CT and ASD.