Evidence for altered trisynaptic circuitry in schizophrenic hippocampus
Evidence for altered trisynaptic circuitry in schizophrenic hippocampus
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DOI：
10.1016/s0006-3223(99)00136-5
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发表时间：
1999-09-01
影响因子：
10.6
通讯作者：
Benes, FM
中科院分区：
文献类型：
--
作者：
Benes, FM
最近的尸检研究表明，精神分裂症(SZ)患者的海马体结构(HIPP)发生了细微的变化。这些变化包括非锥体神经元(NPs)密度降低，GABA(A)增加，但苯二氮卓受体不变，GAD(65)-IR终末增加，特别是在CA3和CA2区。对GABA(A)受体的高分辨率研究进一步表明，CA3区锥体层的去抑制性GABA能活性(即GABA-to-GABA)的降低可能与同一区段的层方向的抑制性调制(即GABA-兴奋性锥体神经元)的减少并存。这些变化可能潜在地涉及对CA2区中间神经元的兴奋性毒性损伤；但是，从现有数据尚不能推断在出生前和出生后生活中诱导这种损伤的确切时间框架。这些发现与SZ患者HIPP异常振荡节律和基础代谢活动增加的报道一致。躁狂抑郁症患者CA2中NPs的减少表明，GABA系统的变化可能与SZ的易感基因无关。相反，这些变化可能与压力等非特定因素有关，这些因素要么在生命早期经历，要么在青春期或成年期经历很长时间。据推测，在建立SZ表型时，可能还存在与其他递质系统相关的变化，生物精神病学1999；46：589-599(C)1999生物精神病学学会。
Recent postmortem studies have demonstrated subtle alterations in the hippocampal formation (HIPP) of patients with schizophrenia (SZ). These changes include a decreased density of nonpyramidal neurons (NPs), an increase of the GABA(A), but not benzodiazepine receptors and a neuroleptic-dose-related increase of GAD(65)-IR terminals, particularly in sectors CA3 and CA2. High resolution studies of the GABA(A) receptor have further suggested that a decrease of disinhibitory GABAergic activity (i.e., GABA-to-GABA) in stratum pyramidale of CA3 may coexist with reduced inhibitory modulation (i.e., GABA-to-excitatory pyramidal neuron) in the stratum oriens of this same sector. These changes could potentially involve excitotoxic damage to interneurons in CA2; but, the precise time frame for the induction of such an injury during pre- versus postnatal life cannot as yet be inferred from the available data. These findings are consistent with reports of abnormal oscillatory rhythms and increased basal metabolic activity in the HIPP of patients with SZ. The fact that patients with manic depression also show a decrease of NPs in CA2 suggests that changes in the GABA system may not be related to a susceptibility gene for SZ. Rather, these alterations could be associated with a nonspecific factor such as stress, experienced either early in life or much later during adolescence or adulthood. Presumably, there are also changes associated in other transmitter systems that may play a more specific role in establishing the SZ phenotype, Biol Psychiatry 1999;46:589-599 (C) 1999 Society of Biological Psychiatry.