Neuroscience
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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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In general, catechins contained in green tea are believed to have positive effects on the human body and mental health. The intake of epigallocatechin gallate (EGCG), a major polyphenol in green tea, is known to be effective for retinal protection; however, whether green tea and/or EGCG affect visual function remains unknown. In the present study, we investigated the effect of green tea and EGCG on visual motion processing by measuring optokinetic responses (OKRs) in young adult and aging mice. ⋯ We found that the OKRs of young and aging mice after green tea intake and after EGCG administration showed higher temporal sensitivity than those of control mice. The visual ability to detect moving objects was enhanced in young and aging mice upon intake of green tea or EGCG. From the above results, the visual motion processing for optokinetic responses by ingesting green tea was enhanced, which may be related to the effect of EGCG.
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Knockdown of Girdin induced apoptosis of glioblastoma cells via the mitochondrion signaling pathway.
Glioblastoma is the most common primary brain tumor with poor survival rate and without effective treatment strategy. However, the influence of Girdin on human glioblastoma and the underlying molecular mechanisms have yet to be uncovered. We mainly investigated the role of Girdin in glioblastoma cells apoptosis. ⋯ Moreover, subcutaneous mouse xenograft model was used to validate the role of Girdin in glioblastoma apoptosis. Consistently, in vivo assays showed that knockdown of Girdin inhibited the growth of the grafted tumor and increased the level of Cyt-C and Bad. These findings demonstrated that knockdown of Girdin may induce Bad expression and reduce Bcl-2 expression by inhibiting the activation of AKT, leading to the release of Cyt-C from mitochondria, thereby promoting glioblastoma cells apoptosis.
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Hypoxic-ischemic brain damage (HIBD) usually induces chronic neurological disorder and even acute death, but effective neuroprotective strategy is still limited. Herein, we performed this study to clarify the mechanism of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) containing microRNA-93 (miR-93) in influencing this damage via regulation of the histone deacetylase 4 (HDAC4)/B-cell lymphoma-2 (Bcl-2) axis. Initially, differentially expressed Bcl-2 was identified in middle cerebral artery occlusion (MCAO), and the upstream regulatory miR-93 and its potential target HDAC4 were also predicted through bioinformatics analysis. ⋯ Of note, miR-93 was found to target HDAC4. Importantly, MSC-derived EVs overexpressing miR-93 suppressed HDAC4 expression and subsequently impeded the apoptosis of OGD-exposed hippocampal neurons in vitro, and also ameliorated HIBD in vivo. Taken together, miR-93 delivered by MSC-derived EVs can ameliorate HIBD by suppressing hippocampal neuron apoptosis through targeting the HDAC4/Bcl-2 axis, a finding which may be of great significance in the treatment of HIBD.
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Despite the presence of multiple pharmacotherapeutic options, incidence rates for depressive disorders continue to rise. Nonpharmacological approaches (e.g., cognitive and behavioral therapies) exhibit encouraging efficacy rates; however, a lack of preclinical models has prevented progress in the identification of relevant neurobiological mechanisms of these approaches. Accordingly, the effort-based reward (EBR) preclinical model exposes rats to response-outcome (R-O) contingencies and provides an opportunity to investigate behavioral clinical approaches. ⋯ Examination of brain-derived neurotrophic factor (BDNF) in the lateral habenula (LHb), a putative neurobiological target for depressive symptoms, revealed lower BDNF immunoreactivity in EBR contingent-trained rats. Females in both training groups exhibited higher dehydroepiandrosterone/cortisol (DHEA/CORT) ratios, suggesting, along with the increased engagement with novel stimulus panels, that female rats may be more responsive to EBR contingency training than males. Together, these results suggest that EBR contingency training offers promise as a preclinical rat model for behavioral therapeutic interventions for depressive symptoms leading to a clearer understanding of putative neurobiological mechanisms.