精神分裂症患者海马区γ-氨基丁酸能中间神经元钙结合蛋白的免疫组化研究

Expression of calcium-binding proteins parvalbumin and calretinin in interneurons of hippocampus in schizophrenia

目的 通过定量分析精神分裂症患者海马区γ 氨基丁酸 (GABA)能中间神经元相对密度的改变 ,探讨其在精神分裂症发病机理中的作用。方法 共 30例患者的脑组织标本 ,其中精神分裂症患者 15例 (精神分裂症组 ) ,无神经或精神疾病史者 15例 (对照组 )。采用免疫组化法结合抗parvalbumin(PV)和抗calretinin(CR)抗体 ,测定精神分裂症组和对照组钙结合蛋白 (CBPs)免疫反应 (IR)阳性细胞在海马本体齿状回和阿蒙角 (Ammon′shorn ,CA1 CA4 )的分布、胞体大小、相对密度及海马亚区面积。结果 与对照组比较 ,精神分裂症组CR IR中间神经元相对密度的差异无显著性 (P >0 0 5 ) ,而PV IR中间神经元相对密度在海马各亚区均严重缺失 ,差异有显著性 (P <0 0 5～ 0 0 0 1) ;其中以男性患者为著 ,与年龄、病程和抗精神病药无显著性相关 (P >0 0 5 )。结论 精神分裂症患者海马区含PV的GABA能抑制性中间神经元亚群缺失 ,似符合早期神经发育异常的病因学假说。

Objectives To determine the relative densities of GABAergic subpopulation defined by calcium binding proteins (CBPs) and to further study the importance of change of GABAergic interneurons on neuropathology in hippocampus in schizophrenia Methods The relative densities and neuronal body size of cells immunoreactive for the CBPs parvalbumin (PV) and calretinin (CR) and area size of hippocampal sub fields as well were determined in hippocampal tissue sections taken from schizophrenic patients and well matched control subjects (15 per group) Results No significant difference in the density of CR IR neurons and the neuronal body size of CR positive neurones was found between groups ( P >0 05) Relative to controls, schizophrenic patients showed a significant and profound deficit in the relative density of PV IR neurons in all hippocampal sub fields ( P < 0 05-0 001) These reductions were more apparent in male than female schizophrenic patients ( P <0 05), and were unrelated to antipsychotic drug treatment, age or duration of illness ( P >0 05) Conclusions The findings provide further evidence to support a profound abnormality of a sub population of GABAergic neurons in the hippocampus in schizophrenia, and is consistent with the etiological hypothesis of neurodevelopment of schizophrenia