Neuroscience
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The objective of the study was to examine whether axotomy and 17β-estradiol affects P2X7 receptor expression and distribution in the hypoglossal nucleus. The left hypoglossal nerve of ovariectomized mice was cut and animals received a single injection of 17β-estradiol (25 μg/100g b.w. in 20% (2-hydroxypropyl)-β-cyclodextrin) or vehicle one hour after axotomy. Mice were sacrificed on day 4 following surgery. ⋯ The CD11b immunoreactive microglia area fraction increased significantly following axotomy, but was not affected by 17β-estradiol. Neither ER alpha, nor beta colocalized with CD11b. Our results suggest that axotomy induces cell-type specific changes in P2X7 receptor expression, which may be directly regulated by 17β-estradiol through ER alpha or beta in neurons, but not in activated microglia.
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Binge eating is defined by the consumption of an excessive amount of food in a short time, reflecting a form of hedonic eating that is not necessarily motivated by caloric need. Foods consumed during a binge are also often high in fat and/or sugar. Ghrelin, signaling centrally via the growth-hormone secretagogue receptor (GHSR), stimulates growth hormone release and appetite. ⋯ GHSR KO mice also had reduced activation of the nucleus accumbens shell, but not core, following HFD consumption. These data support the ability of INT HFD in mice to induce a binge-compensate pattern of intake that emulates select components of binge eating in humans. There also appears to be a role for GHSR signaling in driving HFD consumption under these conditions, potentially via mediation of reward-related circuitry.
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Long noncoding RNAs (lncRNAs) are abundant in the central nervous system and have a key role in brain function as well as many neurological disorders. However, the regulatory function of lncRNAs in the premature brain has not been well studied. This study described the expression profile of lncRNAs in premature mice using microarray technology. 1999 differentially expressed lncRNAs and 955 differentially expressed mRNAs were identified. ⋯ Additionally, the lncRNA-mRNA-network and TF-gene-lncRNA-network were constructed to identify core regulatory lncRNAs and transcription factors. The sex-determining region of Y chromosome (SRY) gene may be a key transcription factor that regulates premature brain development and injury. This study for the first time represents an expression profile of differentially expressed lncRNAs in the premature brain and may provide a novel point of view into the mechanisms of premature brain injury.
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Exposure to blast overpressure (BOP) is associated with behavioral, cognitive, and neuroimaging abnormalities. We investigated the dynamic responses of cortical vasculature and its relation to microglia/macrophage activation in mice using intravital two-photon microscopy following mild blast exposure. We found that blast caused vascular dysfunction evidenced by microdomains of aberrant vascular permeability. ⋯ Repetitive, but not single, BOPs also caused TNFα elevation two weeks post-blast. In addition, following a single BOP we found that aberrantly phosphorylated tau rapidly accumulated in perivascular domains, but cleared within four hours, suggesting it was removed from the perivascular area, degraded, and/or dephosphorylated. Taken together these findings argue that mild blast exposure causes an evolving CNS insult that is initiated by discrete disturbances of vascular function, thereby setting the stage for more protracted and more widespread neuroinflammatory responses.
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The most promising therapeutic approach to finding the cure for devastating demyelinating conditions is the identification of clinically safe pharmacological agents that can promote differentiation of endogenous oligodendrocyte precursor cells (OPCs). Here we show that the breast cancer medication tamoxifen (TMX), with well-documented clinical safety and confirmed beneficial effects in various models of demyelinating conditions, stimulates differentiation of rat glial progenitors to mature oligodendrocytes in vitro. Clinically applicable doses of TMX significantly increased both the number of CNPase-positive oligodendrocytes and protein levels of myelin basic protein, measured with Western blots. ⋯ In contrast to TMXC and 4-hydroxy-TMX, endoxifen also induced astrogliogenesis, but independent of the ER activation. In sum, we showed that the TMX prodrug and its two main metabolites (4-hydroxy-TMX and endoxifen) promote ER-dependent oligodendrogenesis in vitro, not reported before. Given that differentiating effects of TMX were achieved with clinically safe doses, TMX is likely one of the most promising FDA-approved drugs for the possible treatment of demyelinating diseases.