Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cells. 2024 Feb 1;13(3):275. doi: 10.3390/cells13030275.
Cigarette smoking during pregnancy is known to be associated with the incidence of attention-deficit/hyperactive disorder (ADHD). Recent developments in deep learning algorithms enable us to assess the behavioral phenotypes of animal models without cognitive bias during manual analysis. In this study, we established prenatal nicotine exposure (PNE) mice and evaluated their behavioral phenotypes using DeepLabCut and SimBA. We optimized the training parameters of DeepLabCut for pose estimation and succeeded in labeling a single-mouse or two-mouse model with high fidelity during free-moving behavior. We applied the trained network to analyze the behavior of the mice and found that PNE mice exhibited impulsivity and a lessened working memory, which are characteristics of ADHD. PNE mice also showed elevated anxiety and deficits in social interaction, reminiscent of autism spectrum disorder (ASD). We further examined PNE mice by evaluating adult neurogenesis in the hippocampus, which is a pathological hallmark of ASD, and demonstrated that newborn neurons were decreased, specifically in the ventral part of the hippocampus, which is reported to be related to emotional and social behaviors. These results support the hypothesis that PNE is a risk factor for comorbidity with ADHD and ASD in mice.
孕期吸烟与注意力缺陷多动障碍（ADHD）的发生有关。深度学习算法的最新发展使我们能够在手动分析过程中避免认知偏差，评估动物模型的行为表型。在这项研究中，我们建立了产前尼古丁暴露（PNE）小鼠模型，并使用 DeepLabCut 和 SimBA 评估了它们的行为表型。我们优化了 DeepLabCut 的训练参数进行姿势估计，并成功地在自由运动行为中对单只或两只小鼠模型进行了高保真度的标记。我们应用训练好的网络分析了这些小鼠的行为，发现 PNE 小鼠表现出冲动行为和工作记忆减退，这些都是 ADHD 的特征。PNE 小鼠还表现出焦虑增加和社交互动缺陷，这与自闭症谱系障碍（ASD）类似。我们通过评估海马体中的成年神经发生进一步研究了 PNE 小鼠，这是 ASD 的一个病理标志，结果表明新生神经元减少，特别是在海马体的腹侧部分，据报道这与情绪和社交行为有关。这些结果支持了 PNE 是导致 ADHD 和 ASD 共病的风险因素的假说。
