Kolomeets Natalya S, Orlovskaya Diana D, Rachmanova Valentina I, Uranova Natalya A
Laboratory of Clinical Neuropathology, Mental Health Research Center, Zagorodnoe shosse 2, Moscow, 117152, Russia.
Synapse. 2005 Jul;57(1):47-55. doi: 10.1002/syn.20153.
Synapses formed between mossy fibers, the axons of hippocampal dentate granular cells, and the dendrites of CA3 pyramidal neurons are important links within the trisynaptic circuitry. Abnormalities in this circuitry are associated with the failure of schizophrenics to integrate affective experience with higher cognitive function, and with disturbances in memory and spatial learning processes. The abnormalities include reduced size and altered dendritic arborization of CA3 pyramidal neurons. In addition, decreased expression and binding activity of glutamate receptors have been reported, predominantly in the CA3 region of the hippocampus. These findings suggest that there are disturbed neuronal processes and connections in the hippocampus of schizophrenics. An electron microscope morphometric study of synaptic contacts between mossy fiber axon terminals (MFT) and branched dendritic spines of pyramidal neurons in stratum lucidum of the CA3 region of the hippocampus was performed in 10 normal controls and 9 age-matched chronic schizophrenics (postmortem delay 3-9 h). Schizophrenic cases with predominantly positive symptoms had a significantly reduced volume fraction of spines (-35%, P < 0.05), total number of invaginated spines (-47%, P < 0.01), and number of spines forming synapses (-32%, P < 0.05) per MFT compared with the control group. No effects of postmortem delay, age, duration of disease, or neuroleptic exposure were found. These data may reflect decreased efficacy of mossy fiber synapses in the CA3 hippocampal region in schizophrenics with predominantly positive symptoms. These data are in line with the neurodevelopmental hypothesis of schizophrenia.
苔藓纤维（海马齿状颗粒细胞的轴突）与CA3锥体神经元的树突之间形成的突触是三突触回路中的重要连接。该回路的异常与精神分裂症患者无法将情感体验与更高的认知功能整合，以及与记忆和空间学习过程的紊乱有关。这些异常包括CA3锥体神经元的大小减小和树突分支改变。此外，据报道谷氨酸受体的表达和结合活性降低，主要发生在海马体的CA3区域。这些发现表明，精神分裂症患者的海马体中存在神经元过程和连接的紊乱。对10名正常对照者和9名年龄匹配的慢性精神分裂症患者（死后延迟3 - 9小时）进行了海马体CA3区透明层中苔藓纤维轴突终末（MFT）与锥体神经元分支树突棘之间突触接触的电子显微镜形态计量学研究。与对照组相比，以阳性症状为主的精神分裂症患者每个MFT的棘突体积分数显著降低（-35%，P < 0.05），内陷棘突总数显著减少（-47%，P < 0.01），形成突触的棘突数量显著减少（-32%，P < 0.05）。未发现死后延迟、年龄、病程或抗精神病药物暴露的影响。这些数据可能反映了以阳性症状为主的精神分裂症患者海马体CA3区苔藓纤维突触的效能降低。这些数据与精神分裂症的神经发育假说一致。
