Neuroscience
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the 2019 coronavirus disease (COVID-19), has affected more than 20 million people in Brazil and caused a global health emergency. This virus has the potential to affect various parts of the body and compromise metabolic functions. The virus-mediated neural inflammation of the nervous system is due to a storm of cytokines and oxidative stress, which are the clinical features of Alzheimer's disease (AD). ⋯ The cholinergic system, through neurons and the neurotransmitter acetylcholine (ACh), modulates various physiological pathways, such as the response to stress, sleep and wakefulness, sensory information, and the cognitive system. Patients with AD have low concentrations of ACh; hence, therapeutic methods are aimed at adjusting the ACh titers available to the body for maintaining functionality. Herein, we focused on acetylcholinesterase inhibitors, responsible for the degradation of ACh in the synaptic cleft, and muscarinic and nicotinic receptor agonists of the cholinergic system owing to the therapeutic potential of the cholinergic anti-inflammatory pathway in AD associated with SARS-CoV-2 infection.
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Social anxiety is characterized by an intense fear of evaluation from others and/or withdrawal from social situations. Extreme social anxiety can lead to social anxiety disorder. There remains an urgent need to investigate the neural substrates of subclinical social anxiety for early diagnosis and intervention to reduce the risk to develop social anxiety disorder. ⋯ The activation of superficial amygdala and the deactivation of basal forebrain in response to angry condition showed positive correlations with the level of social anxiety. In addition, the resting-state functional connectivity between these two regions was negatively correlated with the level of social anxiety. These results may help to understand the individual difference and corresponding neural underpinnings of social anxiety in the subclinical population, and might provide some insight to develop strategies for early diagnosis and interventions of social anxiety to reduce the risk of deterioration from subclinical to clinical level of social anxiety.
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Aquaporin-4 (AQP4) regulates retinal water homeostasis and participates in retinal oedema pathophysiology. β-dystroglycan (β-DG) is responsible for AQP4 polarization and can be cleaved by matrix metalloproteinase-9 (MMP9). Retinal oedema induced by ischemia-reperfusion (I/R) injury is an early complication. Bumetanide (BU) has potential efficacy against cytotoxic oedema. ⋯ BU suppressed glial responses and mitochondria-mediated apoptotic protein expression, including that of Caspase-3 and Cyto C, raised the Bcl-2/Bax ratio, and lowered the number of apoptotic cells in the retina. Both BU and U0126 downregulated p-ERK and MMP9 expression. Thus, BU treatment suppressed β-DG cleavage, recovered AQP4 polarization partially via inhibiting ERK/MMP9 signaling pathway, and possess potential neuroprotective efficacy in the rat retinal ischemia-reperfusion injury model.
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Cannabinoids regulate analgesia, which has aroused much interest in identifying new pharmacological therapies in the management of refractory pain. Voltage-gated Na+ channels (Navs) play an important role in inflammatory and neuropathic pain. In particular, Nav1.9 is involved in nociception and the understanding of its pharmacology has lagged behind because it is difficult to express in heterologous systems. ⋯ In agreement with the experimental evidence, our computer simulations revealed that ACEA binds Tyr1599 of the local anaesthetics binding site of the hNav1.9, contacting residues that bind cannabinol (CBD) in the NavMs channel. ACEA adopted a conformation remarkably similar to the crystallographic conformation of anandamide on a non-homologous protein, obstructing the Na+ permeation pathway below the selectivity filter to occupy a highly conserved binding pocket at the intracellular side. These results describe a mechanism of action, possibly involved in cannabinoid analgesia.
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Cofilin 1 is an actin depolymerizing protein playing a fundamental role in the turnover of actin filaments specifically in dendritic spines, where it has been associated with structural and functional plasticity processes. Using a differential proteomic approach, we recently identified cofilin 1 as a potential candidate for controlling plasticity levels in the mouse visual cortex. Here, we focus on analyzing the expression of cofilin 1 and of its serine-3 phosphorylated inactive form in the mouse visual cortex during postnatal development and its modulation by visual input. ⋯ By immunohistochemistry, we identified that the phospho-cofilin 1 immunopositive signal is homogeneously expressed along the different layers of the mouse visual cortex and that it increases during postnatal development. Furthermore, monocular deprivation increases the phospho-cofilin 1 signal in the contralateral cortex to the deprived eye during the critical period but not in the adult stage. Altogether, these results suggest that cofilin 1 and its modification by phosphorylation are relevant players in the processes controlling experience-dependent plasticity in the mouse visual cortex.