Genes Brain and Behavior最新文献_第7页

5. Collaborative Study on the Genetics of Alcoholism: Functional genomics 5.酒精中毒遗传学合作研究：功能基因组学。

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-08-02 DOI: 10.1111/gbb.12855

Isabel Gameiro-Ros, Dina Popova, Iya Prytkova, Zhiping P. Pang, Yunlong Liu, Danielle Dick, Kathleen K. Bucholz, Arpana Agrawal, Bernice Porjesz, Alison M. Goate, Xiaoling Xuei, Chella Kamarajan, COGA Collaborators, Jay A. Tischfield, Howard J. Edenberg, Paul A. Slesinger, Ronald P. Hart

{"title":"5. Collaborative Study on the Genetics of Alcoholism: Functional genomics","authors":"Isabel Gameiro-Ros, Dina Popova, Iya Prytkova, Zhiping P. Pang, Yunlong Liu, Danielle Dick, Kathleen K. Bucholz, Arpana Agrawal, Bernice Porjesz, Alison M. Goate, Xiaoling Xuei, Chella Kamarajan, COGA Collaborators, Jay A. Tischfield, Howard J. Edenberg, Paul A. Slesinger, Ronald P. Hart","doi":"10.1111/gbb.12855","DOIUrl":"10.1111/gbb.12855","url":null,"abstract":"Alcohol Use Disorder is a complex genetic disorder, involving genetic, neural, and environmental factors, and their interactions. The Collaborative Study on the Genetics of Alcoholism (COGA) has been investigating these factors and identified putative alcohol use disorder risk genes through genome-wide association studies. In this review, we describe advances made by COGA in elucidating the functional changes induced by alcohol use disorder risk genes using multimodal approaches with human cell lines and brain tissue. These studies involve investigating gene regulation in lymphoblastoid cells from COGA participants and in post-mortem brain tissues. High throughput reporter assays are being used to identify single nucleotide polymorphisms in which alternate alleles differ in driving gene expression. Specific single nucleotide polymorphisms (both coding or noncoding) have been modeled using induced pluripotent stem cells derived from COGA participants to evaluate the effects of genetic variants on transcriptomics, neuronal excitability, synaptic physiology, and the response to ethanol in human neurons from individuals with and without alcohol use disorder. We provide a perspective on future studies, such as using polygenic risk scores and populations of induced pluripotent stem cell-derived neurons to identify signaling pathways related with responses to alcohol. Starting with genes or loci associated with alcohol use disorder, COGA has demonstrated that integration of multimodal data within COGA participants and functional studies can reveal mechanisms linking genomic variants with alcohol use disorder, and potential targets for future treatments.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/5a/GBB-22-e12855.PMC10550792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042569","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}

引用次数: 1

Partner-seeking and limbic dopamine system are enhanced following social loss in male prairie voles (Microtus ochrogaster) 雄性草原田鼠（Microtus ochrogaster）在社交丧失后寻找伴侣的能力和边缘多巴胺系统得到增强

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-07-30 DOI: 10.1111/gbb.12861

Erika M. Vitale, Adrianna Kirckof, Adam S. Smith

{"title":"Partner-seeking and limbic dopamine system are enhanced following social loss in male prairie voles (Microtus ochrogaster)","authors":"Erika M. Vitale, Adrianna Kirckof, Adam S. Smith","doi":"10.1111/gbb.12861","DOIUrl":"10.1111/gbb.12861","url":null,"abstract":"Death of a loved one is recognized as one of life's greatest stresses, and 10%–20% of bereaved individuals will experience a complicated or prolonged grieving period that is characterized by intense yearning for the deceased. The monogamous prairie vole (Microtus ochrogaster) is a rodent species that forms pair bonds between breeding partners and has been used to study the neurobiology of social behaviors and isolation. Male prairie voles do not display distress after isolation from a familiar, same-sex conspecific; however, separation from a bonded female partner increases emotional, stress-related, and proximity-seeking behaviors. Here, we tested the investigatory response of male voles to partner odor during a period of social loss. We found that males who lost their partner spent significantly more time investigating partner odor but not non-partner social odor or food odor. Bachelor males and males in intact pairings did not respond uniquely to any odor. Furthermore, we examined dopamine (DA) receptor mRNA expression in the anterior insula cortex (aIC), nucleus accumbens (NAc), and anterior cingulate (ACC), regions with higher activation in grieving humans. While we found some effects of relationship type on DRD1 and DRD2 expression in some of these regions, loss of a high-quality opposite-sex relationship had a significant effect on DA receptor expression, with pair-bonded/loss males having higher expression in the aIC and ACC compared with pair-bonded/intact and nonbonded/loss males. Together, these data suggest that both relationship type and relationship quality affect reunion-seeking behavior and motivational neurocircuits following social loss of a bonded partner.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12861","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10274164","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}

引用次数: 0

Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain 母性教养和自愿运动行为的选择性繁殖改变了小鼠大脑中 DNA 甲基化和基因表达的模式

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-07-30 DOI: 10.1111/gbb.12858

Sarah E. Latchney, Marcell D. Cadney, Anthony Hopkins, Theodore Garland Jr

{"title":"Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain","authors":"Sarah E. Latchney, Marcell D. Cadney, Anthony Hopkins, Theodore Garland Jr","doi":"10.1111/gbb.12858","DOIUrl":"10.1111/gbb.12858","url":null,"abstract":"Selective breeding has been utilized to study the genetic basis of exercise behavior, but research suggests that epigenetic mechanisms, such as DNA methylation, also contribute to this behavior. In a previous study, we demonstrated that the brains of mice from a genetically selected high runner (HR) line have sex-specific changes in DNA methylation patterns in genes known to be genomically imprinted compared to those from a non-selected control (C) line. Through cross-fostering, we also found that maternal upbringing can modify the DNA methylation patterns of additional genes. Here, we identify an additional set of genes in which DNA methylation patterns and gene expression may be altered by selection for increased wheel-running activity and maternal upbringing. We performed bisulfite sequencing and gene expression assays of 14 genes in the brain and found alterations in DNA methylation and gene expression for Bdnf, Pde4d and Grin2b. Decreases in Bdnf methylation correlated with significant increases in Bdnf gene expression in the hippocampus of HR compared to C mice. Cross-fostering also influenced the DNA methylation patterns for Pde4d in the cortex and Grin2b in the hippocampus, with associated changes in gene expression. We also found that the DNA methylation patterns for Atrx and Oxtr in the cortex and Atrx and Bdnf in the hippocampus were further modified by sex. Together with our previous study, these results suggest that DNA methylation and the resulting change in gene expression may interact with early-life influences to shape adult exercise behavior.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12858","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9897853","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}

引用次数: 0

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency 部分多巴胺转运体缺乏症雄性大鼠的乙醇摄入模式

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-07-17 DOI: 10.1111/gbb.12847

L. B. Kuiper, J. B. Roberts, P. M. Estave, D. Leo, R. R. Gainetdinov, S. R. Jones

{"title":"Patterns of ethanol intake in male rats with partial dopamine transporter deficiency","authors":"L. B. Kuiper, J. B. Roberts, P. M. Estave, D. Leo, R. R. Gainetdinov, S. R. Jones","doi":"10.1111/gbb.12847","DOIUrl":"10.1111/gbb.12847","url":null,"abstract":"Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/−) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/− rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/− rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/− males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824706","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}

引用次数: 0

The impact of early adversity and education on genetic and brain morphological predictors of cognitive ability 早期逆境和教育对认知能力遗传和脑形态预测因子的影响

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-07-04 DOI: 10.1111/gbb.12850

Emma Corley, Laura Fahey, Joan Fitzgerald, Laurena Holleran, Esther Walton, Derek W. Morris, Gary Donohoe

{"title":"The impact of early adversity and education on genetic and brain morphological predictors of cognitive ability","authors":"Emma Corley, Laura Fahey, Joan Fitzgerald, Laurena Holleran, Esther Walton, Derek W. Morris, Gary Donohoe","doi":"10.1111/gbb.12850","DOIUrl":"10.1111/gbb.12850","url":null,"abstract":"Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known about how these factors combine and interact to explain this variation in cognition. To address this, we modelled the relationship between common genetic variation, grey matter volume, early life adversity and education and cognitive ability in a UK Biobank sample of N = 5237 individuals using structural equation modelling. We tested the hypotheses that total grey matter volume would mediate the association between genetic variation and cognitive ability, and that early life adversity and educational attainment would moderate this relationship. Common genetic variation, grey matter volume and early life adversity were each significant predictors in the model, explaining ~15% of variation in cognitive ability. Contrary to our hypothesis, grey matter volume did not mediate the relation between genetic variation and cognition performance. Neither did early life adversity or educational attainment moderate this relation, although educational attainment was observed to moderate the relationship between grey matter volume and cognitive performance. We interpret these findings in terms of the modest explanatory value of currently estimated polygenic scores accounting for variation in cognitive performance (~5%), making potential mediating and moderating variables difficult to confirm.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923818","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}

引用次数: 0

The collaborative study on the genetics of alcoholism: Genetics 关于酗酒遗传学的合作研究：遗传学。

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-06-30 DOI: 10.1111/gbb.12856

Emma C. Johnson, Jessica E. Salvatore, Dongbing Lai, Alison K. Merikangas, John I. Nurnberger, Jay A. Tischfield, Xiaoling Xuei, Chella Kamarajan, Leah Wetherill, COGA Collaborators, John P. Rice, John R. Kramer, Samuel Kuperman, Tatiana Foroud, Paul A. Slesinger, Alison M. Goate, Bernice Porjesz, Danielle M. Dick, Howard J. Edenberg, Arpana Agrawal

{"title":"The collaborative study on the genetics of alcoholism: Genetics","authors":"Emma C. Johnson, Jessica E. Salvatore, Dongbing Lai, Alison K. Merikangas, John I. Nurnberger, Jay A. Tischfield, Xiaoling Xuei, Chella Kamarajan, Leah Wetherill, COGA Collaborators, John P. Rice, John R. Kramer, Samuel Kuperman, Tatiana Foroud, Paul A. Slesinger, Alison M. Goate, Bernice Porjesz, Danielle M. Dick, Howard J. Edenberg, Arpana Agrawal","doi":"10.1111/gbb.12856","DOIUrl":"10.1111/gbb.12856","url":null,"abstract":"This review describes the genetic approaches and results from the family-based Collaborative Study on the Genetics of Alcoholism (COGA). COGA was designed during the linkage era to identify genes affecting the risk for alcohol use disorder (AUD) and related problems, and was among the first AUD-focused studies to subsequently adopt a genome-wide association (GWAS) approach. COGA's family-based structure, multimodal assessment with gold-standard clinical and neurophysiological data, and the availability of prospective longitudinal phenotyping continues to provide insights into the etiology of AUD and related disorders. These include investigations of genetic risk and trajectories of substance use and use disorders, phenome-wide association studies of loci of interest, and investigations of pleiotropy, social genomics, genetic nurture, and within-family comparisons. COGA is one of the few AUD genetics projects that includes a substantial number of participants of African ancestry. The sharing of data and biospecimens has been a cornerstone of the COGA project, and COGA is a key contributor to large-scale GWAS consortia. COGA's wealth of publicly available genetic and extensive phenotyping data continues to provide a unique and adaptable resource for our understanding of the genetic etiology of AUD and related traits.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e9/f4/GBB-22-e12856.PMC10550788.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9843742","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}

引用次数: 2

Rapamycin improves social and stereotypic behavior abnormalities induced by pre-mitotic neuronal subset specific Pten deletion 雷帕霉素改善有丝分裂前神经元亚群特异性Pten缺失引起的社会和刻板行为异常

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-06-28 DOI: 10.1111/gbb.12854

David A. Narvaiz, Suzanne O. Nolan, Gregory D. Smith, Andrew J. Holley, Conner D. Reynolds, Katherine J. Blandin, Phuoc H. Nguyen, Doan L. K. Tran, Joaquin N. Lugo

{"title":"Rapamycin improves social and stereotypic behavior abnormalities induced by pre-mitotic neuronal subset specific Pten deletion","authors":"David A. Narvaiz, Suzanne O. Nolan, Gregory D. Smith, Andrew J. Holley, Conner D. Reynolds, Katherine J. Blandin, Phuoc H. Nguyen, Doan L. K. Tran, Joaquin N. Lugo","doi":"10.1111/gbb.12854","DOIUrl":"10.1111/gbb.12854","url":null,"abstract":"The mechanistic target of rapamycin (mTOR) pathway is a signaling system integral to neural growth and migration. In both patients and rodent models, mutations to the phosphatase and tensin homolog gene (PTEN) on chromosome 10 results in hyperactivation of the mTOR pathway, as well as seizures, intellectual disabilities and autistic behaviors. Rapamycin, an inhibitor of mTOR, can reverse the epileptic phenotype of neural subset specific Pten knockout (NS-Pten KO) mice, but its impact on behavior is not known. To determine the behavioral effects of rapamycin, male and female NS-Pten KO and wildtype (WT) mice were assigned as controls or administered 10 mg/kg of rapamycin for 2 weeks followed by behavioral testing. Rapamycin improved social behavior in both genotypes and stereotypic behaviors in NS-Pten KO mice. Rapamycin treatment resulted in a reduction of several measures of activity in the open field test in both genotypes. Rapamycin did not reverse the reduced anxiety behavior in KO mice. These data show the potential clinical use of mTOR inhibitors by showing its administration can reduce the production of autistic-like behaviors in NS-Pten KO mice.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12854","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923802","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}

引用次数: 0

Extensive characterization of a Williams syndrome murine model shows Gtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior Williams综合征小鼠模型的广泛表征显示gtf2ird1介导的选择性感觉运动任务的拯救，但对增强的社会行为没有影响

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-06-27 DOI: 10.1111/gbb.12853

Kayla R. Nygaard, Susan E. Maloney, Raylynn G. Swift, Katherine B. McCullough, Rachael E. Wagner, Stuart B. Fass, Krassimira Garbett, Karoly Mirnics, Jeremy Veenstra-VanderWeele, Joseph D. Dougherty

{"title":"Extensive characterization of a Williams syndrome murine model shows Gtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior","authors":"Kayla R. Nygaard, Susan E. Maloney, Raylynn G. Swift, Katherine B. McCullough, Rachael E. Wagner, Stuart B. Fass, Krassimira Garbett, Karoly Mirnics, Jeremy Veenstra-VanderWeele, Joseph D. Dougherty","doi":"10.1111/gbb.12853","DOIUrl":"10.1111/gbb.12853","url":null,"abstract":"Williams syndrome is a rare neurodevelopmental disorder exhibiting cognitive and behavioral abnormalities, including increased social motivation, risk of anxiety and specific phobias along with perturbed motor function. Williams syndrome is caused by a microdeletion of 26–28 genes on chromosome 7, including GTF2IRD1, which encodes a transcription factor suggested to play a role in the behavioral profile of Williams syndrome. Duplications of the full region also lead to frequent autism diagnosis, social phobias and language delay. Thus, genes in the region appear to regulate social motivation in a dose-sensitive manner. A “complete deletion” mouse, heterozygously eliminating the syntenic Williams syndrome region, has been deeply characterized for cardiac phenotypes, but direct measures of social motivation have not been assessed. Furthermore, the role of Gtf2ird1 in these behaviors has not been addressed in a relevant genetic context. Here, we have generated a mouse overexpressing Gtf2ird1, which can be used both to model duplication of this gene alone and to rescue Gtf2ird1 expression in the complete deletion mice. Using a comprehensive behavioral pipeline and direct measures of social motivation, we provide evidence that the Williams syndrome critical region regulates social motivation along with motor and anxiety phenotypes, but that Gtf2ird1 complementation is not sufficient to rescue most of these traits, and duplication does not decrease social motivation. However, Gtf2ird1 complementation does rescue light-aversive behavior and performance on select sensorimotor tasks, perhaps indicating a role for this gene in sensory processing or integration.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12853","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209779","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}

引用次数: 0

Genetic and environmental influences on one-trial conditioned context aversion in mice 遗传和环境对小鼠单试验条件情境厌恶的影响

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-06-26 DOI: 10.1111/gbb.12857

Çınar Furkan İlhan, Gonzalo P. Urcelay, Sezen Kışlal

{"title":"Genetic and environmental influences on one-trial conditioned context aversion in mice","authors":"Çınar Furkan İlhan, Gonzalo P. Urcelay, Sezen Kışlal","doi":"10.1111/gbb.12857","DOIUrl":"10.1111/gbb.12857","url":null,"abstract":"Anticipatory nausea (AN) is caused by an association between contextual cues and the experience of nausea (the side effects of chemotherapy or radiation treatment) and it develops predominantly in female patients undergoing chemotherapy. Preclinical studies in rodents show that the administration of an illness-inducing agent in the presence of novel contextual cues can cause conditioned context aversion (CCA) and this has been proposed to model AN. The literature also suggests that brief pre-exposure to a novel context prior to shock delivery is critical in the development of contextual fear conditioning in rodents (a phenomenon known as Immediate Shock Deficit), but this has not been assessed in CCA. The aim of present study was to develop a CCA paradigm to assess this in outbred (CD1) and inbred (C57BL/6J) mice and evaluate potential sex differences. The results revealed that a single conditioning trial in which a distinctive context was paired with LiCl-induced illness was sufficient to elicit a conditioned response in both female and male CD1 outbred mice, but not in C57BL/6J inbred mice. In addition, CCA was facilitated when animals had prior experience with the context. Finally, outbred female mice showed longer and more robust retention of CCA than male mice, which parallels clinical findings. The results indicate the importance of using CD1 outbred mice as an animal model of AN as well as examining sex differences in the CCA paradigm. Similar findings in humans encourage the future use of this novel CCA preclinical mouse model.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ed/a4/GBB-22-e12857.PMC10393421.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9915041","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}

引用次数: 0

Spontaneous allelic variant in deafness–blindness gene Ush1g resulting in an expanded phenotype 聋盲基因Ush1g的自发等位变异导致表型扩大

IF 2.5 4区心理学

Genes Brain and Behavior Pub Date : 2023-06-16 DOI: 10.1111/gbb.12849

Vladimir Vartanian, Jocelyn F. Krey, Paroma Chatterjee, Allison Curtis, Makayla Six, Sean P. M. Rice, Sherri M. Jones, Harini Sampath, Charles N. Allen, Renee C. Ryals, R. Stephen Lloyd, Peter G. Barr-Gillespie

{"title":"Spontaneous allelic variant in deafness–blindness gene Ush1g resulting in an expanded phenotype","authors":"Vladimir Vartanian, Jocelyn F. Krey, Paroma Chatterjee, Allison Curtis, Makayla Six, Sean P. M. Rice, Sherri M. Jones, Harini Sampath, Charles N. Allen, Renee C. Ryals, R. Stephen Lloyd, Peter G. Barr-Gillespie","doi":"10.1111/gbb.12849","DOIUrl":"10.1111/gbb.12849","url":null,"abstract":"Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target‐specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards‐walking behavior in open‐field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1gbw/bw null mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner‐ear hair‐cell function, including a complete lack of auditory brainstem responses and vestibular‐evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell's kinocilial links. Consistent with other Usher type 1 models, Ush1gbw/bw mice had no substantial retinal degeneration compared with Ush1gbw/+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene.","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/a6/GBB-22-e12849.PMC10393423.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977941","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}

引用次数: 0