Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats

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Maciel , I D S , Sales , A J , Casarotto , P C , Castrén , E , Biojone , C & Joca , S R L 2022 , ' Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats ' , European Journal of Neuroscience , vol. 55 , no. 9-10 , pp. 2421-2434 . https://doi.org/10.1111/ejn.15042

Title: Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats
Author: Maciel, Izaque de Sousa; Sales, Amanda J.; Casarotto, Plinio C.; Castrén, Eero; Biojone, Caroline; Joca, Samia R. L.
Contributor organization: Neuroscience Center
Helsinki Institute of Life Science HiLIFE
Date: 2022-05
Language: eng
Number of pages: 14
Belongs to series: European Journal of Neuroscience
ISSN: 0953-816X
DOI: https://doi.org/10.1111/ejn.15042
URI: http://hdl.handle.net/10138/346195
Abstract: It has been postulated that the activation of NMDA receptors (NMDAr) and nitric oxide (NO) production in the hippocampus is involved in the behavioral consequences of stress. Stress triggers NMDAr-induced calcium influx in limbic areas, such as the hippocampus, which in turn activates neuronal NO synthase (nNOS). Inhibition of nNOS or NMDAr activity can prevent stress-induced effects in animal models, but the molecular mechanisms behind this effect are still unclear. In this study, cultured hippocampal neurons treated with NMDA or dexamethasone showed an increased of DNA methyltransferase 3b (DNMT3b) mRNA expression, which was blocked by pre-treatment with nNOS inhibitor n(omega)-propyl-l-arginine (NPA). In rats submitted to the Learned Helplessness paradigm (LH), we observed that inescapable stress increased DNMT3b mRNA expression at 1h and 24h in the hippocampus. The NOS inhibitors 7-NI and aminoguanidine (AMG) decreased the number of escape failures in LH and counteracted the changes in hippocampal DNMT3b mRNA induced in this behavioral paradigm. Altogether, our data suggest that NO produced in response to NMDAr activation following stress upregulates DNMT3b in the hippocampus.
Subject: DNA methylation
DNMT3b
epigenetics
learned helplessness
nitric oxide
SOLUBLE GUANYLATE-CYCLASE
LEARNED HELPLESSNESS
GENE-EXPRESSION
NEUROTROPHIC FACTOR
EPIGENETIC MECHANISMS
ANTIDEPRESSANT ACTION
BEHAVIORAL-RESPONSES
SIGNALING PATHWAY
ANIMAL-MODEL
METHYLATION
3112 Neurosciences
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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