Goldberg Lisa R, Kutlu Munir Gunes, Zeid Dana, Seemiller Laurel R, Gould Thomas J
Department of Biobehavioral Health, Penn State University, University Park, Pennsylvania, USA.
Genes Brain Behav. 2021 Apr 2:e12734. doi: 10.1111/gbb.12734.
Cognitive deficits, such as disrupted learning, are a major symptom of nicotine withdrawal. These deficits are heritable, yet their genetic basis is largely unknown. Our lab has developed a mouse model of nicotine withdrawal deficits in learning, using chronic nicotine exposure via osmotic minipumps and fear conditioning. Here, we utilized the BXD genetic reference panel to identify genetic variants underlying nicotine withdrawal deficits in learning. Male and female mice (n = 6-11 per sex per strain, 31 strains) received either chronic saline or nicotine (6.3 mg/kg per day for 12 days), and were then tested for hippocampus-dependent learning deficits using contextual fear conditioning. Quantitative trait locus (QTL) mapping analyses using GeneNetwork identified a significant QTL on Chromosome 4 (82.13 Mb, LRS = 20.03, p < 0.05). Publicly available hippocampal gene expression data were used to identify eight positional candidates (Snacpc3, Mysm1, Rps6, Plaa, Lurap1l, Slc24a2, Hacd4, Ptprd) that overlapped with our behavioral QTL and correlated with our behavioral data. Overall, this study demonstrates that genetic factors impact cognitive deficits during nicotine withdrawal in the BXD recombinant inbred panel and identifies candidate genes for future research.
认知缺陷，如学习障碍，是尼古丁戒断的主要症状。这些缺陷具有遗传性，但其遗传基础在很大程度上尚不清楚。我们实验室通过渗透微型泵慢性尼古丁暴露和恐惧条件反射，建立了一种尼古丁戒断学习缺陷的小鼠模型。在此，我们利用BXD遗传参考面板来识别学习中尼古丁戒断缺陷背后的遗传变异。雄性和雌性小鼠（每个品系每种性别n = 6 - 11只，共31个品系）接受慢性生理盐水或尼古丁（每天6.3 mg/kg，持续12天）处理，然后使用情境恐惧条件反射测试海马体依赖性学习缺陷。使用GeneNetwork进行的数量性状位点（QTL）图谱分析在4号染色体上确定了一个显著的QTL（8
