The selective nNOS inhibitor 5-methyl-thiocitrulline (SMTC) impaired cued and contextual LTM in WT mice. The NO donor molsidomine recovered contextual LTM but had no effect on cued LTM in nNOS KO mice. Re-exposure to the visual cue
24 h posttraining elicited freezing response and a marked increase in plasma corticosterone levels in WT but not nNOS KO mice. The expression of CREB phosphorylation (Ser-133) was significantly higher in naive nNOS KO mice than in WT counterparts, and pharmacological modulators of NO had significant effects on levels of CREB phosphorylation and expression. These findings suggest that visual cue-dependent LTM is impaired in nNOS KO mice, and aberrant modulation of CREB in the absence of the nNOS gene may hinder cued and contextual LTM formation. (C) 2011 IBRO. Published SB203580 datasheet by Elsevier Ltd. All rights reserved.”
“The hippocampus is a brain region that is particularly susceptible to structural and functional changes in response to chronic stress. Recent literature has focused on changes in gene transcription mediated by post-translational modifications of histones in response to stressful stimuli. Chronic variable stress (CVS) is a rodent model that mimics certain symptoms of depression in humans. Given that stress exhibits distinct effects on the cells of the sub-regions of the hippocampus,
we investigated changes in histone acetylation in the CA1, CA3, and dentate gyrus (DG) of the hippocampus in response to CVS. Western blotting revealed a significant decrease in acetylation of histone 4 (H4) at Lys12 in CA3 and DG of CVS animals compared to control animals. Furthermore, phospho-acetyl H3 (Lys9/Ser10)
SN-38 price was also decreased in the CA3 and DG regions of the hippocampus of CVS animals. In addition, since histone deacetylases (HDACs) contribute to the acetylation state of histones, we investigated the effects of two HDAC inhibitors, sodium butyrate, a class I and II global HDAC inhibitor, and sirtinol, a class III sirtuin inhibitor, on acetylation of histone 3 (H3) and H4. Application of HDAC inhibitors to hippocampus slices from control and CVS animals revealed increased histone acetylation in CVS animals, suggesting that levels of histone deacetylation by Cetuximab in vivo HDACs were higher in the CVS animals compared to control animals. Interestingly, histone acetylation in response to sirtinol was selectively increased in the slices from the CVS animals, with very little effect of sirtuin inhibitors in slices from control animals. In addition, sirtuin activity was increased specifically in CA3 and DG of CVS animals. These results suggest a complex and regionally-specific pattern of changes in histone acetylation within the hippocampus which may contribute to stress-induced pathology. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction.
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