Stolp Helen, Neuhaus Ain, Sundramoorthi Rohan, Molnár Zoltán
Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, UK.
Front Psychiatry. 2012 Jun 12;3:50. doi: 10.3389/fpsyt.2012.00050. eCollection 2012.
Cortical development is a complex amalgamation of proliferation, migration, differentiation, and circuit formation. These processes follow defined timescales and are controlled by a combination of intrinsic and extrinsic factors. It is currently unclear how robust and flexible these processes are and whether the developing brain has the capacity to recover from disruptions. What is clear is that there are a number of cognitive disorders or conditions that are elicited as a result of disrupted cortical development, although it may take a long time for the full pathophysiology of the conditions to be realized clinically. The critical window for the manifestation of a neurodevelopmental disorder is prolonged, and there is the potential for a complex interplay between genes and environment. While there have been extended investigations into the genetic basis of a number of neurological and mental disorders, limited definitive associations have been discovered. Many environmental factors, including inflammation and stress, have been linked to neurodevelopmental disorders, and it may be that a better understanding of the interplay between genes and environment will speed progress in this field. In particular, the development of the brain needs to be considered in the context of the whole materno-fetal unit as the degree of the metabolic, endocrine, or inflammatory responses, for example, will greatly influence the environment in which the brain develops. This review will emphasize the importance of extending neurodevelopmental studies to the contribution of the placenta, vasculature, cerebrospinal fluid, and to maternal and fetal immune response. These combined investigations are more likely to reveal genetic and environmental factors that influence the different stages of neuronal development and potentially lead to the better understanding of the etiology of neurological and mental disorders such as autism, epilepsy, cerebral palsy, and schizophrenia.
皮质发育是增殖、迁移、分化和神经回路形成的复杂融合。这些过程遵循特定的时间尺度，并受内在和外在因素的共同控制。目前尚不清楚这些过程的稳健性和灵活性如何，以及发育中的大脑是否有能力从干扰中恢复。清楚的是，有许多认知障碍或病症是由皮质发育中断引起的，尽管这些病症的完整病理生理学在临床上可能需要很长时间才能显现出来。神经发育障碍表现的关键窗口延长，并且基因与环境之间可能存在复杂的相互作用。虽然已经对许多神经和精神障碍的遗传基础进行了广泛研究，但发现的明确关联有限。许多环境因素，包括炎症和压力，都与神经发育障碍有关，更好地理解基因与环境之间的相互作用可能会加快该领域的进展。特别是，大脑的发育需要在整个母胎单位的背景下考虑，因为例如代谢、内分泌或炎症反应的程度将极大地影响大脑发育的环境。本综述将强调将神经发育研究扩展到胎盘、脉管系统、脑脊液以及母体和胎儿免疫反应的贡献的重要性。这些综合研究更有可能揭示影响神经元发育不同阶段的遗传和环境因素，并有可能更好地理解自闭症、癫痫、脑瘫和精神分裂症等神经和精神障碍的病因。
