Dept Psychiatry, University of Colorado at Denver and Health Sciences Center, 13001 E. 17th Pl., Campus Box F546, Aurora, CO 800045, USA.
Prog Neurobiol. 2010 Feb 9;90(2):263-75. doi: 10.1016/j.pneurobio.2009.10.008. Epub 2009 Oct 21.
The hippocampal formation plays a critical role in cognitive function. The developmental events that shape the hippocampal formation are continuing to be elucidated and their implications for brain function are emerging as well as applying those advances to interventions that have important possibilities for the treatment of brain dysfunction. The story told in this chapter is about the use of the in oculo transplant method to illuminate intrinsic and extrinsic features that underlie the development of the dentate gyrus and adjacent hippocampus and the role of one molecule in the hippocampus and schizophrenia. Schizophrenia, originally conceptualized as a dysfunction in dopaminergic neurotransmission, is now known to involve multiple neuronal systems. Dysfunction of hippocampal neurons is emerging as one of its signature pathological features. Basic insights into the development and function of hippocampal interneurons form the basis of a new treatment initiative for this illness. Evidence for the role of the alpha 7-nicotinic acetylcholine receptor in the development and function of these neurons in rodents has led to human trials of nicotinic agonists for cognitive dysfunction in schizophrenia and the possibility of improving hippocampal development in children at risk for schizophrenia by perinatal supplementation with choline, which can act as an alpha 7-nicotinic acetylcholine receptor agonist.
海马结构在认知功能中起着关键作用。目前仍在深入研究塑造海马结构的发育事件,及其对大脑功能的影响,并将这些进展应用于干预措施,为治疗大脑功能障碍提供了重要的可能性。本章讲述的是利用眼内移植方法来阐明内在和外在特征,这些特征是齿状回和相邻海马区发育的基础,以及海马区和精神分裂症中一种分子的作用。精神分裂症最初被认为是多巴胺能神经传递功能障碍,现在已知涉及多个神经元系统。海马神经元功能障碍正成为其标志性病理特征之一。对海马中间神经元发育和功能的基本认识为这种疾病的新治疗方案奠定了基础。在啮齿动物中,α7-烟碱型乙酰胆碱受体在这些神经元的发育和功能中的作用的证据,导致了人类对精神分裂症认知功能障碍的烟碱激动剂的临床试验,以及通过围产期补充胆碱来改善精神分裂症高危儿童的海马发育的可能性,胆碱可以作为α7-烟碱型乙酰胆碱受体激动剂。