Evans Maya M, Hing Benjamin W Q, Weber Matthew A, Maurer Sara V, Baig Ahmed I, Kim Grace S, Anema Samantha L, Ellerbroek Rhett M, Sivakumar Kartik, Michaelson Jacob J, Narayanan Nandakumar S, Stevens Hanna E
Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, 52242, USA.
Iowa Neuroscience Institute, Iowa City, IA, 52242, USA.
bioRxiv. 2024 Dec 27:2024.12.27.627207. doi: 10.1101/2024.12.27.627207.
Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring. We observed enhanced motor learning and earlier response times on an interval timing task, with accompanying changes in time-related medium spiny neuron (MSN) activity. We performed adult dorsal striatal single-cell RNA sequencing following prenatal stress which revealed differentially expressed genes (DEGs) in multiple cell types; downregulated DEGs were enriched for ribosome and translational pathways consistently in MSN subtypes, microglia, and somatostatin neurons. DEGs in MSN subtypes over-represented ASD risk genes and were enriched for synapse-related processes. These results provide insights into striatal alterations relevant to neurodevelopmental disorders.
孕期母亲压力，即产前压力，是后代神经发育障碍的一个风险因素，包括自闭症谱系障碍（ASD）。在ASD中，背侧纹状体表现出与症状严重程度相关的异常，但对于可能起作用的背侧纹状体细胞和分子机制，我们的认识还存在空白。利用小鼠模型，我们研究了产前压力如何影响成年后代的纹状体依赖性行为。我们观察到在间隔计时任务中运动学习增强且反应时间提前，同时与时间相关的中等棘状神经元（MSN）活动也发生了变化。我们在产前压力后对成年背侧纹状体进行单细胞RNA测序，结果揭示了多种细胞类型中差异表达基因（DEG）；在MSN亚型、小胶质细胞和生长抑素神经元中，下调的DEG一致地富集于核糖体和翻译途径。MSN亚型中的DEG过度代表了ASD风险基因，并且富集于与突触相关的过程。这些结果为与神经发育障碍相关的纹状体改变提供了见解。
