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“Social stress has been linked to several neuropsychiatric diseases, including depression, which is a debilitating disease that has genetic, environmental, and epigenetic underpinnings.

This study examined the effects of repeated social defeat on both depressive-like behaviors and histone acetylation in the hippocampus, amygdala, and dorsal prefrontal cortex of male Sprague-Dawley rats.

Subjects were exposed to four consecutive social defeats. Depressive-like behaviors were assayed in the sucrose preference, forced swim, contextual fear, and social Belinostat approach and avoidance tests. Histone H3 and H4 acetylation in the hippocampus, amygdala, and

prefrontal cortex were examined by Western blots under basal conditions and at several time points. We also investigated the potential involvement of N-methyl-d-aspartic acid (NMDA) receptors and glucocorticoid receptors (GR) by injecting respective antagonists prior to each social

defeat and examining their effect on histone acetylation in the hippocampus.

Social defeat resulted in behavioral changes in the forced swim, social avoidance, and contextual fear tests nearly 6 weeks after defeat, with no change in sucrose preference. Additionally, histone H3 acetylation was increased in the hippocampus 30 min following the last defeat and was not blocked by antagonism of either NMDA or GR receptors. There were no changes in histone H4 acetylation.

These results indicate that social defeat

induces several long-lasting depressive-like behaviors in rats and induces a significant, short-lived enough increase in H3 acetylation in GSK2879552 price the hippocampus, although the underlying mechanism behind this change warrants further investigation.”
“beta-Catenin is a unique intracellular protein functioning as an integral component of the cell-cell adherens complex and a principal signaling protein mediating canonical Wnt signaling. Little is known about its function in adult kidneys in the normal physiologic state or after acute kidney injury (AKI). To study this, we generated conditional knockout mice in which the beta-catenin gene was specifically disrupted in renal tubules (Ksp-beta-cat-/-). These mice were phenotypically normal with no appreciable defects in kidney morphology and function. In the absence of beta-catenin, gamma-catenin functionally substituted for it in E-cadherin binding, thereby sustaining the integrity of epithelial adherens junctions in the kidneys. In AKI induced by ischemia reperfusion or folic acid, the loss of tubular beta-catenin substantially aggravated renal lesions. Compared with controls, Ksp-beta-cat-/- mice displayed higher mortality, elevated serum creatinine, and more severe morphologic injury. Consistently, apoptosis was more prevalent in kidneys of the knockout mice, which was accompanied by increased expression of p53 and Bax, and decreased phosphorylated Akt and survivin.