Neuroscience
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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.
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The global burden of neurodegenerative disorders has increased substantially over the past 2 decades due to rising rates of population aging. Although neurodegenerative disorders differ in their clinical presentation, the underlying pathobiological processes are largely shared. Oxidative stress, among other mechanisms, is strongly implicated in neurodegenerative disorders and aging, and can potentially be targeted by antioxidative agents. ⋯ Furthermore, it stimulated the activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. In conclusion, curcumin appears to be a promising compound for phytomedicine. However, due to some concerns about its efficacy, further targeted experiments are needed to identify its exact molecular targets and pathways responsible for its antioxidant effects.
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Chemokines are important regulators of immune, inflammatory, and neuronal responses in peripheral and central pain pathway. The aim of this study was to investigate whether chemokine (C-X-C motif) ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) involve in the development of bone cancer pain (BCP) and the regulation of morphine analgesia in rats. The change of pain behaviors in BCP rats were measured by testing paw withdrawal threshold (PWT). ⋯ While blocking the activation of p-p38, p-ERK and p-AKT, morphine analgesia was enhanced. These results suggest CXCL13 participated in bone cancer pain and opposed morphine analgesia via p38, ERK and AKT pathways. It may be a target to enhance pain management in cancer pain patients.