Neuroscience
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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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Response time (RT) distributions are histograms of the observed RTs for discriminative choices, comprising a rich source of empirical information to study perceptual processes. The drift-diffusion model (DDM), a mathematical formulation predicting decision tasks, reproduces the RT distributions, contributing to our understanding of these processes from a theoretical perspective. Notably, although the mouse is a popular model system for studying brain function and behavior, little is known about mouse perceptual RT distributions, and their description from an information-accumulation perspective. ⋯ The large number of empirical observations that we collected for this study allowed us to achieve accurate convergence for the model fit. Therefore, changes in the experimental conditions were mirrored by changes in model parameters, suggesting the participation of relevant brain areas in the decision-making process. This approach could help interpret future studies involving attention, discrimination, and learning in adult mice.
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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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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.