Hatanaka Yusuke, Kabuta Tomohiro, Wada Keiji
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and PsychiatryTokyo, Japan; Department of Neurology, Graduate School of Medicine, Kyoto UniversityKyoto, Japan.
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo, Japan.
Front Neurosci. 2017 Feb 6;11:35. doi: 10.3389/fnins.2017.00035. eCollection 2017.
Adverse maternal environment during gestation and lactation can have negative effects on the developing brain that persist into adulthood and result in behavioral impairment. Recent studies of human and animal models suggest epidemiological and experimental association between disturbances in maternal environments during brain development and the occurrence of neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, anxiety, depression, and neurodegenerative diseases. In this review, we summarize recent advances in understanding the effects of maternal metabolic and hormonal abnormalities on the developing brain by focusing on the dynamics of dendritic spine, an excitatory postsynaptic structure. We discuss the abnormal instability of dendritic spines that is common to developmental disorders and neurological diseases. We also introduce our recent studies that demonstrate how maternal obesity and hyperandrogenism leads to abnormal development of neuronal circuitry and persistent synaptic instability, which results in the loss of synapses. The aim of this review is to highlight the links between abnormal maternal environment, behavioral impairment in offspring, and the dendiric spine pathology of neuropsychiatric disorders.
孕期和哺乳期的不良母体环境会对发育中的大脑产生负面影响，这种影响会持续到成年并导致行为障碍。最近对人类和动物模型的研究表明，大脑发育过程中母体环境的干扰与神经精神疾病的发生之间存在流行病学和实验性关联，这些疾病包括自闭症谱系障碍、注意力缺陷多动障碍、精神分裂症、焦虑症、抑郁症和神经退行性疾病。在这篇综述中，我们通过关注树突棘（一种兴奋性突触后结构）的动态变化，总结了在理解母体代谢和激素异常对发育中大脑影响方面的最新进展。我们讨论了发育障碍和神经疾病中常见的树突棘异常不稳定性。我们还介绍了我们最近的研究，这些研究表明母体肥胖和高雄激素血症如何导致神经元回路的异常发育和持续的突触不稳定性，进而导致突触丧失。这篇综述的目的是强调异常母体环境、后代行为障碍以及神经精神疾病的树突棘病理学之间的联系。
