Disrupted-in-schizophrenia1 (DISC1) L100P mutation alters synaptic transmission and plasticity in the hippocampus and causes recognition memory deficits.
Disrupted-in-schizophrenia1 (DISC1) L100P mutation alters synaptic transmission and plasticity in the hippocampus and causes recognition memory deficits.
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精神分裂症中断1 (DISC1) L100P突变改变海马突触传递和可塑性并导致识别记忆缺陷
DOI：
10.1186/s13041-016-0270-y
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发表时间：
2016-10-12
期刊：
影响因子：
3.6
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Cui L;Sun W;Yu M;Li N;Guo L;Gu H;Zhou Y
精神分裂症中断易感基因1(DISC1)是精神分裂症、双相情感障碍和抑郁症等一系列具有共同认知障碍的精神疾病的候选易感基因。在这里，我们报告了DISC1 L100P纯合子突变体表现出正常的焦虑和抑郁样行为，但损害了对象识别，这是通过给予非典型抗精神病药物氯氮平来防止的。Ca~(2+)图像分析显示，谷氨酸引起的海马脑片L100P胞浆[Ca~(2+)]升高受到抑制。L100P突变片表现出齿状回(DG)兴奋性突触传递(sEPSCs和mEPSCs)减少和海马CA1区长时程增强受损。L100P突变不改变兴奋性突触标志物PSD95和突触素-1的蛋白表达，也不改变原代培养海马神经元的树突形态。我们的研究结果提示，DISC1 L100P突变小鼠海马区异常突触传递和可塑性的存在可能扰乱了陈述性信息处理，并导致了识别缺陷。
Disrupted-in-schizophrenia 1(DISC1) is a promising candidate susceptibility gene for a spectrum of psychiatric illnesses that share cognitive impairments in common, including schizophrenia, bipolar disorder and major depression. Here we report that DISC1 L100P homozygous mutant shows normal anxiety- and depression-like behavior, but impaired object recognition which is prevented by administration of atypical antipsychotic drug clozapine. Ca2+ image analysis reveals suppression of glutamate-evoked elevation of cytoplasmic [Ca2+] in L100P hippocampal slices. L100P mutant slices exhibit decreased excitatory synaptic transmission (sEPSCs and mEPSCs) in dentate gyrus (DG) and impaired long-term potentiation in the CA1 region of the hippocampus. L100P mutation does not alter proteins expression of the excitatory synaptic markers, PSD95 and synapsin-1; neither does it changes dendrites morphology of primary cultured hippocampal neurons. Our findings suggest that the existence of abnormal synaptic transmission and plasticity in hippocampal network may disrupt declarative information processing and contribute to recognition deficits in DISC1 L100P mutant mice.
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DOI：
10.1073/pnas.0706900104
发表时间：
2007-11-13
影响因子：
11.1
作者：
Li, Weidong;Zhou, Yu;Cannon, Tyrone D.
通讯作者：
Cannon, Tyrone D.
DOI：
10.1186/1744-9081-10-45
发表时间：
2014-12-08
期刊：
Behavioral and brain functions : BBF
影响因子：
--
作者：
Arime Y;Fukumura R;Miura I;Mekada K;Yoshiki A;Wakana S;Gondo Y;Akiyama K
通讯作者：
Akiyama K
影响因子：
3.7
作者：
Chandran JS;Kazanis I;Clapcote SJ;Ogawa F;Millar JK;Porteous DJ;Ffrench-Constant C
通讯作者：
Ffrench-Constant C
影响因子：
11
作者：
Camargo, L. M.;Collura, V.;Brandon, N. J.
通讯作者：
Brandon, N. J.
影响因子：
2
作者：
Jessberger, Sebastian;Clark, Robert E.;Gage, Fred H.
通讯作者：
Gage, Fred H.