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Journal article
Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex
Neurobiology of stress, v 10, pp 100164-100164
01 Feb 2019
PMID: 31193575
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Brain endocannabinoids (eCB), acting primarily via the cannabinoid type 1 receptor (CB1r), are involved in the regulation of many physiological processes, including behavioral responses to stress. A significant neural target of eCB action is the stress-responsive norepinephrine (NE) system, whose dysregulation is implicated in myriad psychiatric and neurodegenerative disorders. Using Western blot analysis, the protein expression levels of a key enzyme in the biosynthesis of the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol lipase-alpha (DGL-alpha), and two eCB degrading enzymes monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) were examined in a mouse model that lacks the NE-synthesizing enzyme, dopamine beta-hydroxylase (D beta H-knockout, KO) and in rats treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4). In the prefrontal cortex (PFC), DGL-alpha protein expression was significantly increased in male and female D beta H-KO mice (P < 0.05) compared to wild-type (WT) mice. D beta H-KO male mice showed significant decreases in FAAH protein expression compared to WT male mice. Consistent with the D beta H-KO results, DGL-alpha protein expression was significantly increased in male DSP-4-treated rats (P < 0.05) when compared to saline-treated controls. MGL and FAAH protein expression levels were significantly increased in male DSP-4 treated rats compared to male saline controls. Finally, we investigated the anatomical distribution of MGL and FAAH in the NE containing axon terminals of the PFC using immunoelectron microscopy. MGL was predominantly within presynaptic terminals while FAAH was localized to postsynaptic sites. These results suggest that the eCB system may be more responsive in males than females under conditions of NE perturbation, thus having potential implications for sex-specific treatment strategies of stress-related psychiatric disorders.
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Details
- Title
- Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex
- Creators
- M. A. Urquhart - Drexel UniversityJ. A. Ross - Drexel UniversityB. A. S. Reyes - Drexel UniversityM. Nitikman - Drexel UniversityS. A. Thomas - Translational Therapeutics (United States)K. Mackie - Indiana UniversityE. J. Van Bockstaele - Drexel University
- Publication Details
- Neurobiology of stress, v 10, pp 100164-100164
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- R01 DA020129 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01DA020129 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000477761300030
- Scopus ID
- 2-s2.0-85065146587
- Other Identifier
- 991019185110804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences