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Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder
Substance use disorders are a debilitating group of psychiatric disorders with a high degree of comorbidity with major depressive disorder. Sleep and circadian rhythm disturbances are commonly reported in people with substance use disorder and major depression and associated with increased risk of r...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489843/ https://www.ncbi.nlm.nih.gov/pubmed/36161151 http://dx.doi.org/10.3389/fnins.2022.903941 |
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author | Valeri, Jake O’Donovan, Sinead M. Wang, Wei Sinclair, David Bollavarapu, Ratna Gisabella, Barbara Platt, Donna Stockmeier, Craig Pantazopoulos, Harry |
author_facet | Valeri, Jake O’Donovan, Sinead M. Wang, Wei Sinclair, David Bollavarapu, Ratna Gisabella, Barbara Platt, Donna Stockmeier, Craig Pantazopoulos, Harry |
author_sort | Valeri, Jake |
collection | PubMed |
description | Substance use disorders are a debilitating group of psychiatric disorders with a high degree of comorbidity with major depressive disorder. Sleep and circadian rhythm disturbances are commonly reported in people with substance use disorder and major depression and associated with increased risk of relapse. Hippocampal somatostatin signaling is involved in encoding and consolidation of contextual memories which contribute to relapse in substance use disorder. Somatostatin and clock genes also have been implicated in depression, suggesting that these molecules may represent key converging pathways involved in contextual memory processing in substance use and major depression. We used hippocampal tissue from a cohort of subjects with substance use disorder (n = 20), subjects with major depression (n = 20), subjects with comorbid substance use disorder and major depression (n = 24) and psychiatrically normal control subjects (n = 20) to test the hypothesis that expression of genes involved in somatostatin signaling and clock genes is altered in subjects with substance use disorder. We identified decreased expression of somatostatin in subjects with substance use disorder and in subjects with major depression. We also observed increased somatostatin receptor 2 expression in subjects with substance use disorder with alcohol in the blood at death and decreased expression in subjects with major depression. Expression of the clock genes Arntl, Nr1d1, Per2 and Cry2 was increased in subjects with substance use disorder. Arntl and Nr1d1 expression in comparison was decreased in subjects with major depression. We observed decreased expression of Gsk3β in subjects with substance use disorder. Subjects with comorbid substance use disorder and major depression displayed minimal changes across all outcome measures. Furthermore, we observed a significant increase in history of sleep disturbances in subjects with substance use disorder. Our findings represent the first evidence for altered somatostatin and clock gene expression in the hippocampus of subjects with substance use disorder and subjects with major depression. Altered expression of these molecules may impact memory consolidation and contribute to relapse risk. |
format | Online Article Text |
id | pubmed-9489843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94898432022-09-22 Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder Valeri, Jake O’Donovan, Sinead M. Wang, Wei Sinclair, David Bollavarapu, Ratna Gisabella, Barbara Platt, Donna Stockmeier, Craig Pantazopoulos, Harry Front Neurosci Neuroscience Substance use disorders are a debilitating group of psychiatric disorders with a high degree of comorbidity with major depressive disorder. Sleep and circadian rhythm disturbances are commonly reported in people with substance use disorder and major depression and associated with increased risk of relapse. Hippocampal somatostatin signaling is involved in encoding and consolidation of contextual memories which contribute to relapse in substance use disorder. Somatostatin and clock genes also have been implicated in depression, suggesting that these molecules may represent key converging pathways involved in contextual memory processing in substance use and major depression. We used hippocampal tissue from a cohort of subjects with substance use disorder (n = 20), subjects with major depression (n = 20), subjects with comorbid substance use disorder and major depression (n = 24) and psychiatrically normal control subjects (n = 20) to test the hypothesis that expression of genes involved in somatostatin signaling and clock genes is altered in subjects with substance use disorder. We identified decreased expression of somatostatin in subjects with substance use disorder and in subjects with major depression. We also observed increased somatostatin receptor 2 expression in subjects with substance use disorder with alcohol in the blood at death and decreased expression in subjects with major depression. Expression of the clock genes Arntl, Nr1d1, Per2 and Cry2 was increased in subjects with substance use disorder. Arntl and Nr1d1 expression in comparison was decreased in subjects with major depression. We observed decreased expression of Gsk3β in subjects with substance use disorder. Subjects with comorbid substance use disorder and major depression displayed minimal changes across all outcome measures. Furthermore, we observed a significant increase in history of sleep disturbances in subjects with substance use disorder. Our findings represent the first evidence for altered somatostatin and clock gene expression in the hippocampus of subjects with substance use disorder and subjects with major depression. Altered expression of these molecules may impact memory consolidation and contribute to relapse risk. Frontiers Media S.A. 2022-09-07 /pmc/articles/PMC9489843/ /pubmed/36161151 http://dx.doi.org/10.3389/fnins.2022.903941 Text en Copyright © 2022 Valeri, O’Donovan, Wang, Sinclair, Bollavarapu, Gisabella, Platt, Stockmeier and Pantazopoulos. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Valeri, Jake O’Donovan, Sinead M. Wang, Wei Sinclair, David Bollavarapu, Ratna Gisabella, Barbara Platt, Donna Stockmeier, Craig Pantazopoulos, Harry Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder |
title | Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder |
title_full | Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder |
title_fullStr | Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder |
title_full_unstemmed | Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder |
title_short | Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder |
title_sort | altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489843/ https://www.ncbi.nlm.nih.gov/pubmed/36161151 http://dx.doi.org/10.3389/fnins.2022.903941 |
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