Neuroscience
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In stroke-prone spontaneously hypertensive rats (SHRSP/Izm), ischemia induces swelling of astrocytes, a process that subsequently leads to neuronal death. Following ischemic insult, arginine vasopressin (AVP) can induce edema and l-serine released by astrocytes supports the survival of neuronal cells. The purpose of this study was to examine whether AVP contributed to the regulation of l-serine production following ischemic stroke. ⋯ AVP-mediated enhanced expression of ASCT1 was blocked by the addition of bumetanide. These results suggest that the AVP-mediated attenuated expression of ASCT1 in astrocytes is associated with reduced l-serine production in SHRSP/Izm astrocytes. We hypothesize that reduction of gene expression by AVP might be related to the induction of stroke in the SHRpch1_18 rat strain.
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Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. ⋯ In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund's adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms.
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Neuropathologic processes such as cerebral ischemia can enhance neurogenesis. Angiopoietin-1 (Ang1) emerges as a critical regulator of physiological and pathological angiogenesis during embryonic and postnatal life. Although Ang1 could protect peripheral vasculature from vascular leakage following ischemic injury, the role of Ang1 in long-term neurological recovery after ischemic stroke remains elusive. ⋯ Our results demonstrated that lentivirus-mediated Ang1 gene transfer led to improved neurological behavior and reduced infarction volume, and protected against blood-brain barrier (BBB) leakage in the ischemic rats. In addition, we revealed that these effects of Ang1 are related to the ability of Ang1 to increase vascular density and accelerate endogenous neuronal differentiation. These findings suggest that Ang1 is a promising agent for the treatment of cerebral ischemia.
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Dimebon (dimebolin or latrepirdine), originally developed as an anti-histaminic drug, has been investigated and proposed as a cognitive enhancer for treating neurodegenerative disorders such as Alzheimer's and Huntington's diseases, and more recently schizophrenia. This study was conducted to evaluate the potential neuroprotective effect of dimebon during brain ischemia using rat hippocampal slices subjected to oxygen and glucose deprivation followed by a reoxygenation period (OGD/Reox) or glutamate excitotoxicity. Dimebon, incubated during the OGD/Reox period, caused a concentration -dependent protective effect of hippocampal slices; maximum protection (85%) was achieved at 30μM. ⋯ In the glutamate-induced excitotoxicity model, dimebon also afforded a concentration-dependent protective effect that was significantly higher than that obtained with memantine, a non-competitive N-methyl-d-aspartate (NMDA) antagonist. When changes in the intracellular calcium concentration were evaluated in Fluo-4-loaded rat hippocampal neurons, glutamate-induced calcium transients were reduced by 20% with dimebon. These results suggest that dimebon could counteract different pathophysiological processes during ischemic brain damage and, could therefore, be considered as a novel therapeutic strategy for cerebral ischemia-reoxygenation injury.
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Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. ⋯ Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight.