Matsuo Kazuya, Shinoda Yasuharu, Abolhassani Nona, Nakabeppu Yusaku, Fukunaga Kohji
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Front Psychiatry. 2022 Mar 30;13:859198. doi: 10.3389/fpsyt.2022.859198. eCollection 2022.
Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by repetitive behaviors and social impairments, often accompanied by learning disabilities. It has been documented that the neuropeptide oxytocin (OXT) ameliorates core symptoms in patients with ASD. We recently reported that chronic administration of intranasal OXT reversed social and learning impairments in prenatally valproic acid (VPA)-exposed rats. However, the underlying molecular mechanisms remain unclear. Here, we explored molecular alterations in the hippocampus of rats and the effects of chronic administration of intranasal OXT (12 μg/kg/d). Microarray analyses revealed that prenatal VPA exposure altered gene expression, a part of which is suggested as a candidate in ASD and is involved in key features including memory, developmental processes, and epilepsy. OXT partly improved the expression of these genes, which were predicted to interact with those involved in social behaviors and hippocampal-dependent memory. Collectively, the present study documented molecular profiling in the hippocampus related to ASD and improvement by chronic treatment with OXT.
自闭症谱系障碍（ASD）是一种异质性疾病，其特征为重复行为和社交障碍，常伴有学习障碍。已有文献记载，神经肽催产素（OXT）可改善ASD患者的核心症状。我们最近报道，慢性鼻内给予OXT可逆转产前暴露于丙戊酸（VPA）的大鼠的社交和学习障碍。然而，其潜在的分子机制仍不清楚。在此，我们探究了大鼠海马体中的分子变化以及慢性鼻内给予OXT（12μg/kg/d）的影响。微阵列分析显示，产前VPA暴露改变了基因表达，其中一部分被认为是ASD的候选基因，并且参与包括记忆、发育过程和癫痫在内的关键特征。OXT部分改善了这些基因的表达，这些基因预计与参与社会行为和海马体依赖性记忆的基因相互作用。总体而言，本研究记录了与ASD相关的海马体分子图谱以及OXT慢性治疗的改善作用。
