Genes Brain and Behavior最新文献

{"title":"Polygenic Scores of Executive Function Provide Limited Support for Genetic Confounding With Socio-Economic Measures","authors":"Lucas C. Perry,&nbsp;Nicolas Chevalier,&nbsp;Michelle Luciano","doi":"10.1111/gbb.70030","DOIUrl":"https://doi.org/10.1111/gbb.70030","url":null,"abstract":"<p>Previous work has suggested that genetic confounding is a persistent issue in studies of environmental predictors of executive function (EF). This is largely because controlling for genetic confounding typically requires specialized samples such as twins or adoptees, which are more difficult to recruit. Polygenic scores provide a potential alternative control, scalable to smaller samples and not requiring specialized sample features. The purpose of this study was to determine if polygenic scores of EF could be used to replicate the findings of other genetic confounding studies in a less specialized sample. Confounding models showed evidence for genetic confounding in maternal education, although it was far weaker in magnitude than in other genetically informed studies. However, consistent with previous research, there were no detectable influences of indirect genetic effects on the EF polygenic score, indicating that the detected genetic confounding was likely a true genetic effect. Finally, while environmental factors other than maternal education seemed predictive of EF, confounding models showed that this was best explained by their association with maternal education. Other predictors of EF may thus be confounded environmentally, not just genetically. While polygenic scores are a promising method with a multitude of applications, in their current state they do not replicate the findings of other genetically informed studies of EF. Caution should thus be used when employing them to study genetic confounding in EF.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Onset Memory Deficit of WMI Rats Compared to Their Nearly Isogenic WLIs Is Reversed by Enriched Environment in Females","authors":"Michelle T. Ji,&nbsp;Katherine J. Przybyl,&nbsp;Aspen M. Harter,&nbsp;Mariya Nemesh,&nbsp;Sophia T. Jenz,&nbsp;Anna Yamazaki,&nbsp;Chris Kim,&nbsp;Megan K. Mulligan,&nbsp;Hao Chen,&nbsp;Eva E. Redei","doi":"10.1111/gbb.70027","DOIUrl":"https://doi.org/10.1111/gbb.70027","url":null,"abstract":"<p>The underlying mechanisms of early onset memory deficit remain poorly understood. We tested the hypothesis that environmental enrichment (EE) can attenuate early-onset cognitive decline in a novel genetic model, the Wistar Kyoto More Immobile (WMI) inbred rat strain, which manifests the risk factors of enhanced stress reactivity and depression-like behavior compared to its nearly isogenic control, the Wistar Kyoto Less Immobile strain (WLI). Middle-aged (12 months) WMI females exhibited dramatically diminished fear and spatial memory in the contextual fear conditioning and Morris Water Maze paradigms, respectively, compared to young females of both strains and to middle-aged WLI females. Middle-aged WMI males showed a lesser, but significant, age-induced deficit. EE from 6 to 12 months of age completely reversed the memory deficits in middle-aged WMI females and reversed age-induced decreases in plasma levels of estradiol. RNA sequencing from female hippocampi revealed significant strain, age, and enrichment-induced differentially expressed genes. Among these, solute carrier family 35, member A4 (<i>Slc35a4</i>) and potassium inwardly rectifying channel, subfamily J, member 2 (<i>Kcnj2</i>) were confirmed to show hippocampal expression changes parallel to that of memory in the WMI. These genes have critical roles in the integrated stress response, cellular metabolism, and the effects of stress on neurovascular coupling, respectively. Pathway analyses revealed the involvement of oxidative phosphorylation and mitochondrial dysfunction in the hippocampal processes of aging and EE-induced reversal. These findings underscore the critical involvement of molecular stress responses in early-onset memory decline and suggest potential therapeutic targets for age-related cognitive impairment.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differing Genetics of Saline and Cocaine Self-Administration in the Hybrid Mouse Diversity Panel","authors":"Arshad H. Khan,&nbsp;Jared R. Bagley,&nbsp;Nathan LaPierre,&nbsp;Carlos Gonzalez-Figueroa,&nbsp;Tadeo C. Spencer,&nbsp;Mudra Choudhury,&nbsp;Xinshu Xiao,&nbsp;Eleazar Eskin,&nbsp;James D. Jentsch,&nbsp;Desmond J. Smith","doi":"10.1111/gbb.70029","DOIUrl":"https://doi.org/10.1111/gbb.70029","url":null,"abstract":"<p>To identify genes that regulate the response to the potentially addictive drug cocaine, we performed a control experiment using genome-wide association studies (GWASs) and RNA-Seq of a panel of inbred and recombinant inbred mice undergoing intravenous self-administration of saline. A linear mixed model increased statistical power for the analysis of the longitudinal behavioral data, which was acquired over 10 days. A total of 145 loci were identified for saline compared to 17 for the corresponding cocaine GWAS. Only one locus overlapped. Transcriptome-wide association studies (TWASs) using RNA-Seq data from the nucleus accumbens and medial frontal cortex identified <i>5031434O11Rik</i> and <i>Zfp60</i> as significant for saline self-administration. Two other genes, <i>Myh4</i> and <i>Npc1</i>, were nominated based on proximity to loci for multiple endpoints or a <i>cis</i> locus regulating expression. All four genes have previously been implicated in locomotor activity, despite the absence of a strong relationship between saline taking and distance traveled in the open field. Our results indicate a distinct genetic basis for saline and cocaine self-administration, and suggest some common genes for saline self-administration and locomotor activity.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and Genetic Differences in Behavioral Engagement of Crossed High Alcohol-Preferring and Low Alcohol-Preferring Mice","authors":"Phillip Starski,&nbsp;Addyson Siegle,&nbsp;Danielle White,&nbsp;Bea Paras,&nbsp;Christy Tham,&nbsp;Maribel Hernandez,&nbsp;Alecsander Zareb,&nbsp;Nicholas Grahame,&nbsp;Stephen L. Boehm 2nd,&nbsp;Frederic Hopf","doi":"10.1111/gbb.70026","DOIUrl":"https://doi.org/10.1111/gbb.70026","url":null,"abstract":"<p>Excessive levels of alcohol consumption play a major role in numerous alcohol-related harms, including a heightened risk of developing problematic drinking behaviors. Those who develop alcohol use disorder (AUD) often struggle with persistent difficulties in controlling their drinking, experience withdrawal symptoms, and engage in risky behaviors that pose danger to themselves and others. Advances in treating AUD may be supported by identifying specific cognitive and emotional factors that drive excessive alcohol consumption. Recognizing reliable behavioral biomarkers is instrumental in assessing the risk of developing alcohol problems and preventative care strategies. This study investigates innate behavioral differences associated with genetic predisposition for alcohol use by comparing crossed high alcohol-preferring (cHAP) and low alcohol-preferring (LAP) mice. Since there have been links between heightened impulsivity and excessive alcohol use, we hypothesized that cHAP mice would exhibit higher levels of impulsivity compared to LAPs. No significant differences were found in impulsivity between the mouse lines or sexes. cHAPs adapted to shorter stimulus durations (SDs), whereas LAPs showed a marked decline in correct responses and an increase in omission rates as task difficulty increased. Significant sex differences within the cHAP line were found, with females demonstrating higher accuracy, lower correct latency, and increased perseveration. This behavior points to potential sex-specific neural activation in cognitive processing areas. Future studies should explore salient brain regions to understand their roles in behavioral regulation and sex-specific responses to challenges. This study provides a foundation for exploring the interaction of genetic predisposition, sex differences, and neural mechanisms in alcohol preference and behavior.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mutation in the Transmembrane Domain of Adenylate Cyclase 3 Impairs Enzymatic Function to Cause Sex-Specific Depression- and Anxiety-Like Behaviors and Food Seeking in a Rat Model","authors":"Mackenzie K. Fitzpatrick,&nbsp;Christina Dyson,&nbsp;Angela Beeson,&nbsp;Leighelle Adrian,&nbsp;Glen Marrs,&nbsp;Michael Grzybowski,&nbsp;Jason Klotz,&nbsp;Aron M. Geurts,&nbsp;Rong Chen,&nbsp;Jeffrey L. Weiner,&nbsp;Leah C. Solberg Woods","doi":"10.1111/gbb.70028","DOIUrl":"https://doi.org/10.1111/gbb.70028","url":null,"abstract":"<p>We have previously demonstrated that a transmembrane domain mutation in <i>Adenylate cyclase 3</i> (<i>Adcy3</i>) causes increased adiposity and negative emotion-like behaviors in a rat model. We set out to replicate and expand upon our previous study by conducting comprehensive behavioral testing, and we also investigated the molecular changes that result from this mutation. Rats with a mutation in the second transmembrane helix of ADCY3 (Adcy3^mut/mut) and wild-type rats were fed a high-fat diet for 12 weeks. We measured body weight, body composition, and depression-like and anxiety-like behaviors using the following tests: sucrose splash test, sucrose preference test, forced swim test, open field test, elevated plus maze, successive alleys test, and novelty-suppressed feeding. We also measured serum leptin levels, hypothalamic cyclic AMP (cAMP) production, and membrane fraction ADCY3 content. Adcy3^mut/mut male and female rats had increased adiposity. Adcy3^mut/mut males showed increased despair- and anxiety-like behaviors, food seeking, and higher leptin levels relative to wild-type males. Adcy3^mut/mut females showed only mildly increased anxiety-like behaviors relative to wild-type females. Adcy3^mut/mut rats of both sexes had decreased cAMP production in the hypothalamus, with no changes in ADCY3 content in the membrane fraction. We conclude that the transmembrane domain of ADCY3 plays a critical role in regulating adiposity and behavior, as well as cAMP production. There were key differences between males and females for the observed phenotypes. This study supports the idea that <i>Adcy3</i> contributes to emotion-like behaviors and potentially mental health disorders, and that the transmembrane domain of ADCY3 is important for protein function.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Insights Into the Relationship Between the Gut Microbiome and Host Genome in Posttraumatic Stress Disorder","authors":"Michaela A. O'Hare,&nbsp;Carlien Rust,&nbsp;Stefanie Malan-Müller,&nbsp;Walter Pirovano,&nbsp;Christopher A. Lowry,&nbsp;Matsepo Ramaboli,&nbsp;Leigh L. van den Heuvel,&nbsp;Soraya Seedat,&nbsp;PGC-PTSD Microbiome Workgroup,&nbsp;Sian M. J. Hemmings","doi":"10.1111/gbb.70025","DOIUrl":"https://doi.org/10.1111/gbb.70025","url":null,"abstract":"<p>Posttraumatic stress disorder (PTSD) may develop following trauma exposure; however, not all trauma-exposed individuals develop PTSD, suggesting the presence of susceptibility and resilience factors. The gut microbiome and host genome, which are interconnected, have been implicated in the aetiology of PTSD. However, their interaction has yet to be investigated in a South African population. Using genome-wide genotype data and 16S rRNA (V4) gene amplicon sequencing data from 53 trauma-exposed controls and 74 PTSD cases, we observed no significant association between the host genome and summed abundance of <i>Mitsuokella, Odoribacter, Catenibacterium</i> and <i>Olsenella</i>, previously reported as associated with PTSD status in this cohort. However, <i>PROM2</i> rs2278067 T-allele was significantly positively associated with the summed relative abundance of these genera, but only in individuals with PTSD and not trauma-exposed controls (<i>p</i> &lt; 0.014). Polygenic risk scores generated using genome-wide association study summary statistics from the PGC-PTSD Overall Freeze 2 were not predictive of gut microbial composition in this cohort. These preliminary results suggest a potential role for the interaction between genetic variation and gut microbial composition in the context of PTSD, underscoring the need for further investigation.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Cognitive Flexibility With Preserved Learning in an Amyloid Precursor Protein Knock-In Mouse Model of Amyloidopathy","authors":"Julie R. Dumont,&nbsp;Paul A. S. Sheppard,&nbsp;Chris Fodor,&nbsp;M. Alexander Coto,&nbsp;Sabrina Yang,&nbsp;Takashi Saito,&nbsp;Takaomi C. Saido,&nbsp;R. Jane Rylett,&nbsp;Marco A. M. Prado,&nbsp;Timothy J. Bussey,&nbsp;Lisa M. Saksida,&nbsp;Vania F. Prado","doi":"10.1111/gbb.70024","DOIUrl":"https://doi.org/10.1111/gbb.70024","url":null,"abstract":"<p>Alzheimer's disease is a debilitating neurodegenerative condition characterized by amyloid beta plaques and tau neurofibrillary tangles, which leads to progressive cognitive decline. Several new mouse models of fast amyloid deposition have been generated with compound mutations, but how these affect high-level cognitive function is still not fully understood. Four cohorts of a second-generation amyloid precursor protein knock-in mouse model, <i>App</i>^{NL-G-F/NL-G-F}, which develops aggressive amyloidopathy, were compared with two different control groups that do not produce plaques (<i>App</i>^NL/NL and wildtype littermates), on touchscreen-based tests of learning and cognitive flexibility. <i>App</i>^{NL-G-F/NL-G-F} mice learned to discriminate between two visual stimuli during the pairwise visual discrimination (PVD) task but were impaired when the reward contingencies were reversed (the PVR task). Analyses of the correction trials indicated perseverative behavior. One cohort was further tested on the touchscreen Extinction test, which isolates the ability to withhold responding to a previously rewarded stimulus. The <i>App</i>^{NL-G-F/NL-G-F} mice extinguished their responding no differently than the <i>App</i>^NL/NL control group. These results indicate that compound mutations in <i>App</i> driving fast accumulation of plaques in this mouse model impair cognitive flexibility and may serve as a preclinical target for putative therapeutic drugs.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin C Transport Deficiency Alters Striatal Dopamine Gene Expression and Metabolism in YAC128 Huntington Disease Mice","authors":"Adriana A. Tienda,&nbsp;Fiona E. Harrison,&nbsp;Jordyn M. Wilcox","doi":"10.1111/gbb.70023","DOIUrl":"https://doi.org/10.1111/gbb.70023","url":null,"abstract":"<p>Neurodegeneration in Huntington disease (HD) contributes to dopaminergic system dysfunction via the loss of striatal medium spiny neurons expressing dopamine receptors. Given the key role for ascorbic acid (vitamin C) in dopamine synthesis and neurotransmission, we investigated whether mild cellular ascorbate deficiency accelerates dopaminergic dysfunction in the development of HD pathology and behavioral deficits. YAC128 mice expressing mutant human huntingtin were crossed with SVCT2^+/− mice, which carry a heterozygous knockout of the sodium-dependent vitamin C transporter, to generate mice with approximately 30% decreased neuronal vitamin C as well as progressive changes in dopamine signaling. Behavioral and neurochemical outcomes were assessed at early disease stages. At 14 and 20 weeks, YAC128 and SVCT2^+/− YAC128 mice showed similar deficits in grip strength, locomotor activity, and rotarod performance compared to controls, suggesting modest ascorbate deficiency did not accelerate motor phenotypes. Gene expression analysis revealed six significantly upregulated genes in the striatum of SVCT2^+/− YAC128 mice, including those involved in dopamine synthesis, packaging, and transport. Notably, striatal dopamine and serotonin and their metabolites were decreased in both single mutant mouse lines (YAC128 and SVCT2^+/−) but without a compounding effect of the double mutation (SVCT2^+/− YAC128). These results indicate that while moderate ascorbate deficiency may not worsen early behavioral phenotypes in the YAC128 model, it does impact dopamine system regulation at the molecular level. These findings highlight the potential importance of ascorbate in modifying disease progression and suggest that humans with HD, who cannot synthesize ascorbate, may be particularly vulnerable to vitamin C deficiency effects on dopamine dynamics.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Cacna1c Expression Produces Anhedonic Reactions to Palatable Sucrose in Rats: No Interactions With Juvenile or Adult Stress","authors":"Patricia Gasalla,&nbsp;Kerrie L. Thomas,&nbsp;Lawrence Wilkinson,&nbsp;Jeremy Hall,&nbsp;Dominic Michael Dwyer","doi":"10.1111/gbb.70021","DOIUrl":"https://doi.org/10.1111/gbb.70021","url":null,"abstract":"<p>Genetic variation in <i>CACNA1C</i>, which encodes the alpha-1 subunit of Ca_v1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia, bipolar disorder, and major depression. Here we investigated the impact of mutations of one copy of <i>Cacna1c</i> (leading to low gene dosage of <i>Cacna1c</i>) on rats' hedonic responses to palatable sucrose (assessed using the analysis of consumption microstructure). In addition, we also investigated the effects of combining either juvenile or adult stress with the manipulation of <i>Cacna1c</i>. Across three experiments, <i>Cacna1c</i>^+/− rats displayed attenuated hedonic reactions to sucrose compared to wild-type littermate controls, despite the <i>Cacna1c</i>^+/− rats retaining sensitivity to sucrose concentration in terms of the amount of consumption. Unexpectedly, juvenile stress enhanced rather than reduced hedonic reactions to sucrose, while adult stress did not have clear hedonic effects. The effects of <i>Cacna1c</i> manipulation did not interact with either juvenile or adult stress. The fact that <i>Cacna1c</i>^+/− rats display a clear analogue of anhedonia—a reduction in the positive hedonic reactions normally elicited by highly palatable sucrose—a symptom observed trans-diagnostically across psychiatric disorders linked to <i>CACNA1C</i>, suggests this model may play a valuable role in the translational investigation of anhedonia.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of GDAP1 Gene Correlates With Alcohol Deprivation Effect","authors":"Rona Yarimay,&nbsp;Dominik K. E. Beyer,&nbsp;Annakarina Mundorf,&nbsp;Nadja Freund","doi":"10.1111/gbb.70022","DOIUrl":"https://doi.org/10.1111/gbb.70022","url":null,"abstract":"<p>Alcohol addiction is a widespread disease, and the exact causes and consequences are still not fully determined. Neurotransmitters and neuronal circuits are not only the target structure of alcohol and responsible for its direct effects but also play a central role in the development of addiction. A gene that has been linked to alcohol use disorder in recent studies is the <i>ganglioside-induced differentiation-associated protein 1 (GDAP1)</i> gene. The present study focuses on the hippocampus, a brain region particularly vulnerable to alcohol and rich in <i>Gdap1</i> gene expression. Using an established drinking model, alcohol drinking behavior was induced in adult male Long Evans rats. After 6 weeks of voluntary alcohol intake, followed by 2 weeks of deprivation, the animals were divided into two groups based on the alcohol deprivation effect (ADE). <i>Gdap1</i> gene expression was measured with real-time PCR in the hippocampus. Results reveal significantly decreased mRNA expression in the high ADE group compared to the low ADE group. This decrease was specifically detected within the cornu ammonis 3 (CA3) region. <i>Gdap1</i> expression in this region also negatively correlated with ADE in all animals. Taken together, results indicate that <i>Gdap1</i> might not only be associated with alcohol consumption but might even play a role in alcohol dependence.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"24 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}