Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder.
Altered expression of somatostatin signaling molecules and clock genes in the hippocampus of subjects with substance use disorder.
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DOI：
10.3389/fnins.2022.903941
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发表时间：
2022
影响因子：
4.3
通讯作者：
Pantazopoulos, Harry
中科院分区：
文献类型：
--
作者：
Valeri, Jake;O'Donovan, Sinead M.;Wang, Wei;Sinclair, David;Bollavarapu, Ratna;Gisabella, Barbara;Platt, Donna;Stockmeier, Craig;Pantazopoulos, Harry
物质使用障碍是一组使人衰弱的精神疾病，与重度抑郁症高度共存。患有药物滥用障碍和重度抑郁症的人通常会出现睡眠和昼夜节律紊乱，并且与复发风险增加相关。海马生长抑素信号传导参与情境记忆的编码和巩固，这有助于物质使用障碍的复发。生长抑素和时钟基因也与抑郁症有关，这表明这些分子可能代表了物质使用和重度抑郁症的情境记忆处理中涉及的关键聚合途径。我们使用来自物质使用障碍受试者（n = 20）、重度抑郁症受试者（n = 20）、物质使用障碍和重度抑郁症共存受试者（n = 24）和精神正常对照受试者（n = 20）的海马组织来检验物质使用障碍受试者中涉及生长抑素信号和时钟基因的基因表达发生改变的假设。我们发现患有物质使用障碍的受试者和患有重度抑郁症的受试者中生长抑素的表达降低。我们还观察到，在死亡时血液中含有酒精的物质使用障碍受试者中，生长抑素受体 2 表达增加，而在重度抑郁症受试者中，生长抑素受体 2 表达减少。患有物质使用障碍的受试者中时钟基因 Arntl、Nr1d1、Per2 和 Cry2 的表达增加。相比之下，患有重度抑郁症的受试者中 Arntl 和 Nr1d1 的表达有所下降。我们观察到物质使用障碍受试者中 Gsk3β 的表达降低。患有共病物质使用障碍和重度抑郁症的受试者在所有结果指标上都表现出最小的变化。此外，我们观察到患有物质使用障碍的受试者的睡眠障碍史显着增加。我们的研究结果代表了物质使用障碍受试者和重度抑郁症受试者海马中生长抑素和时钟基因表达改变的第一个证据。这些分子表达的改变可能会影响记忆巩固并增加复发风险。
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.
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影响因子：
3.4
作者：
Comasco E;Nordquist N;Göktürk C;Aslund C;Hallman J;Oreland L;Nilsson KW
通讯作者：
Nilsson KW
影响因子：
3.1
作者：
DePoy LM;McClung CA;Logan RW
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Logan RW
影响因子：
9.3
作者：
Calabrese, Francesca;Savino, Elisa;Riva, Marco A.
通讯作者：
Riva, Marco A.
影响因子：
6
作者：
Carter, BL;Tiffany, ST
通讯作者：
Tiffany, ST
影响因子：
5.3
作者：
DePoy, Lauren M.;Becker-Krail, Darius D.;McClung, Colleen A.
通讯作者：
McClung, Colleen A.