Neuroscience
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Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. ⋯ We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission, which is mediated by both presynaptic and postsynaptic mechanisms.
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Mental and neurological illnesses affect one in four people. While genetic linkage analyses have shown an association of nuclear distribution factor E (NDE1, or NudE) and its ohnolog NDE-like 1 (NDEL1, or Nudel) with mental disorders, the cellular mechanisms remain unclear. In the present study, we have demonstrated that Nde1 and Ndel1 are differentially localised in the subventricular zone (SVZ) of the forebrain and the subgranular zone (SGZ) of the hippocampus, two regions where neurogenesis actively occurs in the adult brain. ⋯ In addition, we have shown for the first time that Nde1 is heterogeneously distributed in cortical astrocytes of human brains. Our data indicate that Nde1 and Ndel1 have distinct but overlapping distribution patterns in mouse brain and cultured nerve cells. They may function differently and therefore their dosage changes may contribute to some aspects of mental disorders.
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Physical exercise could exert a neuroprotective effect in both clinical studies and animal experiments. A series of related studies have indicated that physical exercise could reduce infarct volume, alleviate neurological deficits, decrease blood-brain barrier dysfunction, promote angiogenesis in cerebral vascular system and increase the survival rate after ischemic stroke. ⋯ Furthermore, it was demonstrated that exercise training could decrease the blood-brain barrier dysfunction and promote angiogenesis in cerebral vascular system. An awareness of the exercise intervention benefits pre- and post stroke may lead more stroke patients and people with high-risk factors to accept exercise therapy for the prevention and treatment of stroke.
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Brain ischemic tolerance is an endogenous protective mechanism activated by a preconditioning stimulus that is closely related to N-methyl-d-aspartate receptor (NMDAR). Glycine transporter type 1 (GlyT-1) inhibitors potentiate NMDAR and suggest an alternative strategy for brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by sarcosine, a GlyT-1 inhibitor, against global cerebral ischemia and its relation to NMDAR. ⋯ The expression of glycine receptors and the NR1 and NR2A subunits of NMDAR were not affected by sarcosine preconditioning. However, sarcosine preconditioning reduced the expression of the NR2B subunits of NMDAR. In conclusion, these data demonstrate that sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia and this neuroprotective state is associated with changes in glycine transport and reduction of NR2B-containing NMDAR expression.