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Copper mineral: benefits and risks pertaining to hen, issues, and sea food manufacturing.
In addition to its role as a neuronal energy substrate and signaling molecule involved in synaptic plasticity and memory consolidation, recent evidence shows that lactate produces antidepressant effects in animal models. However, the mechanisms underpinning lactate's antidepressant actions remain largely unknown. In this study, we report that lactate reverses the effects of corticosterone on depressive-like behavior, as well as on the inhibition of both the survival and proliferation of new neurons in the adult hippocampus. Furthermore, the inhibition of adult hippocampal neurogenesis prevents the antidepressant-like effects of lactate. Pyruvate, the oxidized form of lactate, did not mimic the effects of lactate on adult hippocampal neurogenesis and depression-like behavior. Finally, our data suggest that conversion of lactate to pyruvate with the concomitant production of NADH is necessary for the neurogenic and antidepressant effects of lactate.Adult hippocampal neurogenesis (AHN) represents a remarkable form of neuroplasticity that has increasingly been linked to the stress response in recent years. selleckchem However, the hippocampus does not itself support the expression of the different dimensions of the stress response. Moreover, the main hippocampal functions are essentially preserved under AHN depletion and adult-born immature neurons (abGNs) have no extrahippocampal projections, which questions the mechanisms by which abGNs influence functions supported by brain areas far from the hippocampus. Within this framework, we propose that through its computational influences AHN is pivotal in shaping adaption to environmental demands, underlying its role in stress response. The hippocampus with its high input convergence and output divergence represents a computational hub, ideally positioned in the brain (1) to detect cues and contexts linked to past, current and predicted stressful experiences, and (2) to supervise the expression of the stress response at the cognitive, affective, behavioral, and physiological levels. AHN appears to bias hippocampal computations toward enhanced conjunctive encoding and pattern separation, promoting contextual discrimination and cognitive flexibility, reducing proactive interference and generalization of stressful experiences to safe contexts. These effects result in gating downstream brain areas with more accurate and contextualized information, enabling the different dimensions of the stress response to be more appropriately set with specific contexts. Here, we first provide an integrative perspective of the functional involvement of AHN in the hippocampus and a phenomenological overview of the stress response. We then examine the mechanistic underpinning of the role of AHN in the stress response and describe its potential implications in the different dimensions accompanying this response.Poverty, as assessed by several socioeconomic (SES) factors, has been linked to worse cognitive performance and reduced cortical brain volumes in children. However, the relative contributions of the various SES factors on brain development and the mediating effects between cognition and brain morphometry have not been investigated. Here we used cross-sectional data from the ABCD Study to evaluate associations among various SES and demographic factors, brain morphometrics, and cognition and their reproducibility in two independent subsamples of 3892 children. Among the SES factors, family income (FI) best explained individual differences in cognitive test scores (stronger for crystallized than for fluid cognition), cortical volume (CV), and thickness (CT). Other SES factors that showed significant associations with cognition and brain morphometrics included parental education and neighborhood deprivation, but when controlling for FI, their effect sizes were negligible and their regional brain patterns were not reproducible. Mediation analyses showed that cognitive scores, which we used as surrogate markers of the children's level of cognitive stimulation, partially mediated the association of FI and CT, whereas the mediations of brain morphometrics on the association of FI and cognition were not significant. These results suggest that lack of supportive/educational stimulation in children from low-income families might drive the reduced CV and CT. Thus, strategies to enhance parental supportive stimulation and the quality of education for children in low-income families could help counteract the negative effects of poverty on children's brain development.The AKT-mTOR signaling transduction pathway plays an important role in neurodevelopment and synaptic plasticity. mTOR is a serine/threonine kinase that modulates signals from multiple neurotransmitters and phosphorylates specific proteins to regulate protein synthesis and cytoskeletal organization. There is substantial evidence demonstrating abnormalities in AKT expression and activity in different schizophrenia (SZ) models. However, direct evidence for dysregulated mTOR kinase activity and its consequences on downstream effector proteins in SZ pathophysiology is lacking. Recently, we reported reduced phosphorylation of mTOR at an activating site and abnormal mTOR complex formation in the SZ dorsolateral prefrontal cortex (DLPFC). Here, we expand on our hypothesis of disrupted mTOR signaling in the SZ brain and studied the expression and activity of downstream effector proteins of mTOR complexes and the kinase activity profiles of SZ subjects. We found that S6RP phosphorylation, downstream of mTOR complex I, is reduced, whereas PKCα phosphorylation, downstream of mTOR complex II, is increased in SZ DLPFC. In rats chronically treated with haloperidol, we showed that S6RP phosphorylation is increased in the rat frontal cortex, suggesting a potential novel mechanism of action for antipsychotics. We also demonstrated key differences in kinase signaling networks between SZ and comparison subjects for both males and females using kinome peptide arrays. We further investigated the role of mTOR kinase activity by inhibiting it with rapamycin in postmortem tissue and compared the impact of mTOR inhibition in SZ and comparison subjects using kinome arrays. We found that SZ subjects are globally more sensitive to rapamycin treatment and AMP-activated protein kinase (AMPK) contributes to this differential kinase activity. Together, our findings provide new insights into the role of mTOR as a master regulator of kinase activity in SZ and suggest potential targets for therapeutic intervention.
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