Neuroscience
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Enhancing the migration and phagocytosis of microglial cells is of great significance for the reducing of the risk of the neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The effect of mouse selenoprotein K (mSELENOK) on the migration and phagocytosis of BV2 microglial cells and its mechanism were studied. The results showed that the over-expression of mSELENOK can increase the migratory and phagocytic abilities of the microglial cells, while the knockdown of mSELENOK can decrease the migratory and phagocytic abilities of the cells. ⋯ Further studies revealed that selenium supplement (Na2SeO3) can increase the expression of mSELENOK in microglial cells significantly. In summary, these data suggest that mSELENOK can increase cytosolic free Ca2+ level of microglial cells by up-regulating the expression of IP3R, thus enhancing the migration and phagocytosis of microglial cells. Our results indicated that mSELENOK is an important selenoprotein, which plays a role in trace element selenium's functions and can enhance the migration and phagocytosis of microglial cells.
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Neuroinflammation is associated with increased vulnerability to diverse psychiatric conditions, including treatment-resistant major depressive disorder (MDD). Here we assessed whether high fat diet (HFD) induced neuroinflammation may be suitable to model a treatment-resistant depressive-like brain state in mice. Male and female mice were fed a HFD for 18 weeks, followed by quantitation of glucose tolerance, inflammatory markers of brain tissue (TNFα, IL-6, IL-1β, Iba-1), neural excitability in the prelimbic cortex (PLC), as well as assessment of emotional reactivity and hedonic behavior in a battery of behavioral tests. ⋯ The behavioral changes were largely resistant to chronic treatment with fluoxetine and desipramine, as well as ketamine. By contrast, retigabine (also known as ezogabine) normalized neural excitability and Ih currents recorded from slices of HFD-treated animals and significantly ameliorated most of the behavioral impairments, without effects in control diet exposed animals. Thus, treatment resistant depressive-like brain states that are associated with chronic neuroinflammation may involve hyperexcitability of pyramidal neurons and may be effectively treated by retigabine.
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Gap junctions mediate electrical coupling between neurons and modulate their firing activity. In mouse neocortical layer 5, the major types of pyramidal neurons organize into cell type-specific microcolumns that exhibit modular neuronal activity. During cortical development, microcolumn neurons are electrically coupled in a cell type-specific manner at the stage of synaptogenesis, forming a dense network of gap junctions. ⋯ This slow synchronization is mediated by electrical transmission that is an order of magnitude slower than that of gap junction-coupled neurons of other types. Theoretical and structural analyses suggested that apical dendrites are a major site of electrical coupling, providing slow electrical transmission. These results suggest that the gap junction network organizes neuronal activity of developing cortical circuit modules with unique slow dynamics.
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Neonatal hypoxic ischemic (HI) brain injury causes lifelong neurologic disability. Therapeutic hypothermia (TH) is the only approved therapy that partially mitigates mortality and morbidity. Therapies specifically targeting HI-induced brain cell death are currently lacking. ⋯ This non-lethal lower dose of GNX-4728 (30 mg/kg, IP) improved the respiratory control ratio of neonatal female HI brain tissue but not in males. Brain injury, assessed histologically with a novel metric approach at 1 and 30 days after HI, was not mitigated by GNX-4728. Our work demonstrates that a small molecule inhibitor of the mPTP has i) an age related toxicity, ii) a sex-related brain mitoprotective profile after HI but iii) this is not sufficient to attenuate forebrain HI neuropathology.
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There is now widespread consensus that social biases often influence actions independently of the actor's intention or awareness. The notion that we are sometimes blind to the origins of our thoughts, attitudes, and behaviors also features prominently in research into domain-general human memory systems, which has a long history of distinguishing between implicit and explicit repercussions of past experience. A shared challenge across these fields of study is thus to identify techniques for effectively managing the contents of our memory stores, particularly those aspects into which we have limited metacognitive insight. ⋯ A second body of work concerns breakthroughs in understanding memory consolidation, which determines the fate of newly encoded memories. We discuss the promise of each of these developments for identifying ways to become better stewards of our social minds. More generally, we suggest that, as with other forms of learning and memory, intentional practice and rehearsal may be critical in learning to minimize unwanted biases.