Neuroscience
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We generated a rat model of sciatic nerve crush injury and characterized the effects of curcumin on sciatic nerve recovery by using behavioral experiments, hematoxylin-eosin staining, toluidine blue staining, and immunohistochemical. Proteomic analysis using tandem mass tagging was performed to determine differentially expressed proteins (DEPs), and GO and KEGG pathway analyses of overlapping DEPs was conducted, following which, qPCR, western blotting, and immunofluorescence were further performed to validate the proteins of interest. Finally, a Schwann cell injury model was used to verify the effect of curcumin on potential targets. ⋯ Curcumin promoted increased expression of ApoD and inhibited the expression of Cyba in vivo and in vitro. These results indicated that curcumin promoted sciatic nerve repair through regulation of various proteins, targets, and pathways. Cyba and ApoD may be potential targets of curcumin in the treatment of SNI.
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Fluoxetine (Flx) is the most commonly used antidepressant to treat major depressive disorder. However, its molecular mechanisms of action are not defined as yet. A comparative proteomic approach was used to identify proteome changes in the prefrontal cortex (PFC) cytosolic and non-synaptic mitochondria (NSM)-enriched fractions of adult male Wistar rats following chronic social isolation (CSIS), a rat model of depression, and Flx treatment in CSIS and control rats, using liquid chromatography online tandem mass spectrometry. ⋯ The presence of cytochrome c in the cytosol may suggest compromised mitochondrial membrane integrity. Flx treatment in CSIS rats downregulated protein involved in oxidative phosphorylation, such as complex III and manganese superoxide dismutase, and upregulated vesicle-mediated transport and synaptic signaling proteins in the cytosol, and neuronal calcium-binding protein 1 in NSM. Our study identified PFC modulated proteins and affected biochemical pathways that may represent potential markers/targets underlying CSIS-induced depression and effective Flx treatment, and highlights the role of protein systems involved in NSM and various metabolic pathways potentially involved in neuronal plasticity.
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Swimming training (ST) can mitigate functional disorders in neurological diseases, but the effect and mechanism of ST in improving the neurological function of intracerebral haemorrhage (ICH) have not been reported. Our study aimed to explore the protective effect of early ST on ICH mice and its relationship with the serine-threonine kinase (Akt)/glycogen synthase kinase 3β (GSK3β) pathway. Our findings showed that the ICH model mice had poor behavioural manifestations in the Y maze test and open field test compared to the ST group and sham group. ⋯ Furthermore, the Akt kinase inhibitor GSK690693 exacerbated neurological impairment, increased the expression of Iba1, GFAP and Bax/Bcl-2, and reversed the anti-apoptotic effects and anti-glia activation of ST, which was associated with the inhibition of p-Akt/Akt and p-GSK3β/GSK3β expression. These results indicated that the protective role of ST in ICH was mediated via the Akt/GSK3β pathway. In conclusion, ST displayed neuroprotection by inhibiting apoptosis and glial activation in ICH mice by activating the Akt/GSK3β signalling pathway.
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Wistar Audiogenic Rats (WAR) is an inbred rodent strain susceptible to acute auditory stimulation-induced seizures. However, spontaneous epileptic seizures (SES) and their associated electroencephalogram (EEG) abnormalities have not been reported in WAR kindled animals. The same is true for naïve WARs (without sound-induced seizures). ⋯ The EEG quantitative analysis showed decreased power of cortical delta, theta and beta oscillations in WAR-S, decreased power of cortical fast gamma (FG) oscillations in WARs, independent of microgyria, and decreased interhemispheric synchrony for delta and FG with stronger coupling in delta and theta-FG oscillations in FL animals. The WARs, regardless of microgyria, had reduced locomotor activity, but only WAR-FL animals had reduced anxiety-like behavior. Microgyria in naïve WARs intensified SWD events associated with behavior arrest that could reflect absence-like seizures and abnormal cortical oscillations, and reduced anxiety-like behavior indicating that WAR-FL could be a reliable model to study epileptogenesis.
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To date, the mechanism of central fatigue during high-intensity exercise has remained unclear. Here we elucidate the central mechanisms of cardiovascular regulation during high-intensity exercise with a focus on the hypothesis that amygdala activation acts to limit maximum exercise performance. In the first of three experiments, we probed the involvement of the central nucleus of the amygdala (CeA) in such regulation. ⋯ We have found that (1) CeA lesions resulted in an increase in the total exercise time and the time at which an abrupt increase in arterial pressure appeared, indicating an apparent suppression of fatigue. (2) We confirmed that high-intensity exercise activated both the PVN-NTS and CeA-NTS pathways. Moreover, we discovered that (3) while stimulation of the CeA or PVN alone both induced pressor responses, their simultaneous stimulation also increased muscle vascular resistance. These results are evidence that cardiovascular responses during high-intensity exercise are affected by CeA activation, which acts to limit maximum exercise performance, and may implicate autonomic control modulating the PVN-NTS pathway via the CeA.