Neuroscience
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Two-pore domain K(+) (K(2P)) channels underlie leak or background potassium conductances in many cells. The Trek subfamily of K(2P) channels, which includes Trek1/Kcnk2 and Trek2/Kcnk10 and has been implicated in depression, nociception, and cognition, exhibits complex regulation and can modulate cell excitability in response to a wide array of stimuli. While alternative translation initiation and alternative splicing contribute to the structural and functional diversity of Trek1, the impact of post-transcriptional modifications on the expression and function of Trek2 is unclear. ⋯ Heterologous expression of Trek2-1p yielded no novel whole-cell currents in transfected human embryonic kidney (HEK) 293 cells. In contrast, expression of Trek2b correlated with robust K(+) currents that were ~fivefold larger than currents measured in cells expressing Trek2a or Trek2c, a difference mirrored by significantly higher levels of Trek2b found at the plasma membrane. This study provides new insights into the molecular diversity of Trek channels and suggests a potential role for the Trek2 amino terminus in channel trafficking and/or stability.
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We have previously demonstrated that glia maturation factor (GMF), a brain-specific protein, isolated, sequenced, and cloned in our laboratory, is a prominent mediator of inflammation in the CNS leading to the death of neurons. In the present study, we demonstrate, for the first time, a significant upregulation of the GMF protein in various regions of Alzheimer's disease (AD) brains compared with age-matched non-demented (ND) control brains. We analyzed AD and ND brain samples by quantitative enzyme-linked immunosorbent assay (ELISA) using a combination of highly specific monoclonal and polyclonal anti-GMF antibodies developed and characterized in our laboratory. ⋯ Our results clearly demonstrate that the GMF protein levels are significantly higher in all AD-affected brain regions than in ND controls. The immunohistochemistry analysis revealed co-localization of GMF with amyloid plaques (AP) and neurofibrillary tangles (NFTs) in AD brains. Our results imply that under conditions of neurodegeneration the expression of GMF is significantly upregulated.
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Previous reports have indicated that adenosine A3 receptor (A3R) knockout mice are more sensitive to ischemic or hypoxic brain injury. The purpose of this study was to examine if suppression of A3R expression is associated with increase in sensitivity to injury induced by a high dose of methamphetamine (Meth). Adult male A3R null mutant (-/-) mice and their controls (+/+) were injected with four doses (2 h apart) of Meth (10 mg/kg) or saline. ⋯ Previous studies have shown that pharmacological suppression of vesicular monoamine transport 2 (VMAT2) by reserpine enhanced Meth toxicity by increasing cytosolic DA and inflammation. A significant reduction in striatal VMAT2 expression was found in -/- mice compared to +/+ mice, suggesting that increase in sensitivity to Meth injury in -/- mice may be related to a reduction in VMAT2 expression in these mice. In conclusion, our data suggest that A3R -/- mice are more sensitive to high doses of Meth.
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An acute injection of brain-derived neurotrophic factor (BDNF) in the hypothalamic ventromedial nucleus (VMN) decreases body weight by reducing feeding and increasing energy expenditure (EE) in animals on standard laboratory chow. Animals have divergent responses to high-fat diet (HFD) exposure, with some developing obesity and others remaining lean. In the current study, we tested the hypothesis that BDNF in the VMN reduces HFD-induced obesity. ⋯ However, BDNF increased EE, spontaneous physical activity, and fat oxidation in the H group, suggesting that BDNF-induced EE elevation contributed to reduction of body weight and fat mass. Chronic VMN BDNF reduced insulin elevation and/or reversed hyperleptinemia. These data suggest that the VMN is an important site of action for BDNF reduction of HFD-induced obesity.
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Here, we established a program of low-intensity aerobic exercise and compared the effects of exercise preoperative, postoperative, and a combination of both pre- and postoperative protocols on recovery from sciatic nerve crush injury in mice using behavioral, biochemical, and morphological assays. Sciatic nerve crush was performed in adult male mice. The animals were submitted to preoperative (for 2 weeks), postoperative (for 2 weeks), and a combination of preoperative-postoperative (for 4 weeks) training protocols. ⋯ In the morphological analysis, the combination exercise subjects presented an increase in fiber and axon diameter, in the myelination degree and in the number of myelinated fibers. The present study showed that pre- and postoperative exercise achieved values for functional and morphological sciatic nerve regeneration that were significantly better than either the preoperative or postoperative protocols. This experimental study suggests that physical exercise can restore motor and nerve function to a substantial degree when performed using a prophylactic and therapeutic approach.