Neuroscience
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It is well established that early blindness results in brain plasticity and behavioral changes in both humans and animals. However, only a few studies have examined the effects of blindness on pain perception. In these studies, pain hypersensitivity was reported in early, but not late, blind humans. ⋯ Moreover, pain hypersensitivity during the formalin test was associated with increased c-Fos immunoreactivity in the amygdala. Furthermore, amygdala volume was larger bilaterally in blind compared with sighted mice. These results indicate that congenitally blind mice show pain hypersensitivity like early blind individuals and suggest that this is due in part to plasticity in the amygdala.
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JLX001, a novel compound with similar structure with cyclovirobuxine D (CVB-D), has been proved to exert therapeutical effects on permanent focal cerebral ischemia. However, the protective effects of JLX001 on cerebral ischemia/reperfusion (I/R) injury and its anti-apoptotic effects have not been reported. We investigated the efficacy of JLX001 in two pharmacodynamic tests (pre-treatment test and post-treatment) with rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). ⋯ Flow cytometry and TdT-mediated dUTP-X nick end labeling (TUNEL) staining demonstrated the anti-apoptotic effects of JLX001 in vitro. Likewise, JLX001 regulated JNK signal pathway in vivo, which was also confirmed by western immunoblotting. Collectively, this study presents the first evidence that JLX001 exerted protective effects against I/R injury by reducing neuronal apoptosis via down-regulating JNK signaling pathway.
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Muscle pain affects approximately 11-24% of the global population. Several studies have shown that exercise is a non-pharmacological therapy to pain control. It has been suggested that the endocannabinoid system is involved in this antinociceptive effect. ⋯ In addition, exercise increased the endocannabinoid anandamide levels and cannabinoid CB2 receptors expression whereas it reduced Iba1 (microglial marker) protein expression as well as pro-inflammatory cytokines (TNF-α and IL-1β) in the spinal cord of mice with inflammatory muscle pain. Swimming training also reduced muscle temperature of carrageen-treated animals. The present study suggests that activation of spinal cannabinoid CB2 receptors and reduction of activated microglia are involved in exercise-induced antinociception.
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The hypothalamus controls food intake and energy expenditure. In rats, maternal exposure to nicotine during breastfeeding alters the hypothalamic circuitry of the adult offspring, resulting in leptin resistance, neuropeptides changes and gliosis. Tobacco smoke exposure during lactation causes greater adiposity, hyperphagia and hyperleptinemia in the adult progeny. ⋯ SE females had lower CART-positive cells (ARC) and lower α-MSH immunostaining intensity (PVN and lateral hypothalamus), with no change of GFAP or IL-6. The protein contents of CX3CR1 (marker of activated microglia) and α7nAChR (anti-inflammatory marker) were not altered in both SE males and females. Neonatal cigarette smoke is deleterious to the hypothalamic circuitry, inducing changes in energy homeostasis favoring hyperphagia and decreased energy expenditure at adulthood in both sexes; however sex-dependent mechanisms were observed.
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The ubiquitin-proteasome system (UPS) controls the degradation of ~90% of short-lived proteins in cells and is involved in activity- and learning-dependent synaptic plasticity in the brain. Calcium/calmodulin dependent protein kinase II (CaMKII) and Protein Kinase A (PKA) can regulate activity of the proteasome. However, there have been a number of conflicting reports regarding under what conditions CaMKII and PKA regulate proteasome activity in the brain. ⋯ Proteasome peptidylglutamyl activity was regulated by CaMKII and PKA activity in the nuclei of amygdala and hippocampus cells in males. However, in females PKA regulated nuclear peptidylglutamyl activity in the amygdala, but not hippocampus. Collectively, these results suggest that CaMKII- and PKA-dependent regulation of proteasome activity in the brain varies significantly across subcellular compartments and between males and females.