Neuroscience
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Understanding the mechanisms that influence brain excitability and synchronization provides hope that epileptic seizures can be controlled. In this scenario, non-synaptic mechanisms have a critical role in seizure activity. The contribution of ion transporters to the regulation of seizure-like activity has not been extensively studied. ⋯ In addition, bumetanide, a selective inhibitor of neuronal Cl(-) uptake mediated by NKCC1, was used to confirm that the NKCC1 increase effectively contributed to NEA changes in the DG. Furthermore, 7 days after KA, prominent NKCC1 staining was identified in the axon initial segments of granule cells, at the exact site where action potentials are preferentially initiated, which endowed these neurons with increased excitability. Taken together, our data suggest a key role of NKCC1 in NEA in the DG.
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Exposure to loud, prolonged sounds (acoustic trauma, AT) leads to the death of both inner and outer hair cells (IHCs and OHCs), death of neurons of the spiral ganglion and degeneration of the auditory nerve. The auditory nerve (8cn) projects to the three subdivisions of the cochlear nuclei (CN), the dorsal cochlear nucleus (DC) and the anterior (VCA) and posterior (VCP) subdivisions of the ventral cochlear nucleus (VCN). There is both anatomical and physiological evidence for plastic reorganization in the denervated CN after AT. ⋯ There was close geographic overlap between the degenerating fibers and activated microglia, consistent with a scavenger role for activated microglia. At the longest survival time, there were still silver-stained fibers but very little staining of activated microglia in overlapping regions. There were, however, activated microglia in the surrounding brainstem and cerebellar white matter.
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Effects of the long-term use of antiepileptic drugs (AEDs) on the brains of patients with epilepsy have been previously reported. The aim of this study was to determine the rapid brain structure remodeling induced by single-dose intravenous AED administration that rules out the potential effects of epilepsy. ⋯ Single-dose intravenous administration of a level of VPA or LEV that mimics clinical use is associated with rapid and reversible VBM-detected GMV or WMV alterations in rhesus monkeys. This finding may provide new insights into the understanding of AED-induced brain structure remodeling and may contribute to our understanding of the brain-level mechanisms and targets of AED action.
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The objective in this study was to test the hypothesis that the GABA-synthesizing enzyme, glutamic acid decarboxylase (Gad67), expressed in striatal neurons plays a key role in dyskinesia induced by L-DOPA (LID) in a rodent model of Parkinson's disease. In light of evidence that the dopamine Drd1a receptor is densely expressed in striatal direct pathway striatal neurons while the orphan G-protein-coupled receptor Gpr88 is densely expressed in striatal direct and indirect pathway striatal neurons, we used a cre-lox strategy to produce two lines of mice that were Gad1 (Gad1 is the gene encoding for Gad67)-deficient in neurons expressing the Drd1a or the Gpr88 receptor. Gad67 loss in Gpr88-expressing neurons mice did not result in gross motor abnormalities while mice with Gad67 loss in Drd1a-expressing neurons were impaired on the Rotarod and the pole test. ⋯ Mice with a Gad67 loss in Gpr88-expressing neurons and control littermates developed abnormal involuntary movements (AIM), a measure of dyskinesia. In contrast, mice with a Gad67 loss in Drd1a-expressing did not develop AIM. The results demonstrate that Gad67 in Drd1a-expressing neurons plays a key role in the development of LID and they support the hypothesis that altered GABAergic neurotransmission in the direct pathway is involved in dyskinesia.
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Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. ⋯ Inhibition of ryanodine receptors by ryanodine or dantrolene also reduced the action of NaHS on EPC amplitudes. Our results indicate that in mammalian neuromuscular synapses endogenously produced H2S increases spontaneously and evoked quantal transmitter release from motor nerve endings without changing the response of nerve endings. The presynaptic effect of H2S appears mediated by intracellular Ca(2+) and cAMP signaling and involves presynaptic ryanodine receptors.