Neuroscience
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Glutamate is the neurotransmitter used at most excitatory synapses in the mammalian brain, including those in the olfactory bulb (OB). There, ionotropic glutamate receptors including N-methyl-d-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) play a role in processes such as reciprocal inhibition and glomerular synchronization. Kainate receptors (KARs) represent another type of ionotropic glutamate receptor, which are composed of five (GluK1-GluK5) subunits. ⋯ The latter finding suggests that KARs, with relatively slow kinetics, may play a role in circuits in which the relatively brief duration of AMPAR-mediated currents limits the role of AMPARs in synaptic transmission (e.g., reciprocal inhibition at dendrodendritic synapses). Collectively, our findings suggest that KARs, including those containing the GluK1 subunit, modulate excitatory and inhibitory transmission in the OB. These data further suggest that KARs participate in the regulation of synaptic circuits that encode odor information.
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It is generally believed that oxidative stress and neuroinflammation are implicated in the pathogenesis of Parkinson's disease (PD). Reduced nicotinamide adenine dinucleotide phosphate (NADPH) has been demonstrated to have potent neuroprotective effects against oxidative stress. In the present research, we investigated if NADPH could offer neuroprotection by inhibiting glia-mediated neuroinflammation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mechanism contributing to PD pathogenesis. ⋯ These effects were diminished by TNF-α neutralizing antibody and NADPH. NADPH reduced motor dysfunction and the loss of dopaminergic (DA) cells induced by MPTP. Therefore, the present study demonstrates that NADPH protects DA neurons by inhibiting oxidative stress and glia-mediated neuroinflammation both in vitro and in vivo, thus suggesting a potential of clinical application for PD and other neurodegenerative diseases.
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2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside (salidroside analog-4g, SalA-4g), has shown neuroprotective prospects for the treatment of ischemic stroke. However, the dose-response and time window study for SalA-4g, and the mechanism of SalA-4g-mediated neuroprotection remain unclear. Here, we systematically investigated the therapeutic time window and dosage of SalA-4g in permanent focal cerebral ischemia in rats. ⋯ Moreover, significant neurological functional recovery was found after SalA-4g administration in long-term functional assays. Further studies suggested that SalA-4g ameliorated neuronal cell death, elevated local glucose metabolism and enhanced the expression level of glucose transporter 1 and 3 in the ipsilateral cortex and striatum. We suggest that data of this study are critical in exploring the clinical application prospects of SalA-4g for the treatment of ischemic stroke.
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Temporomandibular joint (TMJ) is frequently involved with rheumatoid arthritis with a high prevalence that could result in a chronic pain state. Once the disease is established in the joint, the antigen-specific immune reaction initiates a neuro-immune cascade of events that causes sensitization of the central nervous system. This study establishes animal experimental models that evaluate the chronicity of albumin-induced arthritis hypernociception in the TMJ. ⋯ Intra-articular injection of mBSA (10 µg/TMJ/week) during 3 weeks resulted in a persistent inflammatory hypernociception which was characterized by an inflammatory episode characterized by the increased of lymphocytes, macrophages and pro-inflammatory interleukins IL-12 and IL-18. The persistent model of inflammatory hypernociception induced by arthritis in the TMJ elicited protein levels of P2X7 receptors, cathepsin S and fractalkine in the trigeminal subnucleus caudalis. Overall, the results of the present work suggest that a persistent inflammatory hypernociception of albumin-induced arthritis in the TMJ leads to the activation of the central nervous system signaling by P2X7/cathepsin S/fractalkine pathway.
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Downslope walking (DSW) causes H-reflex depression in healthy adults, and thus may hold promise for inducing spinal reflex plasticity in people with Multiple Sclerosis (PwMS). The study purpose was to test the hypothesis that DSW will cause acute depression of spinal excitability in PwMS. Soleus H-reflexes were measured in PwMS (n = 18) before and after 20 min of treadmill walking during three visits. ⋯ DSW evokes short-term spinal plasticity in PwMS, while requiring no greater effort than LW. Our results suggest that PwMS retain the capacity for DSW-induced short-term spinal reflex modulation previously found in healthy adults. These results may provide a foundation for further investigation of long-term effects of DSW on spinal reflex plasticity and functional ability in PwMS.