Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus.
Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social Memory and Synaptic Functions in the Hippocampus.
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青少年孤立与 DISC1 点突变相互作用，损害成年社会记忆和海马突触功能
DOI：
10.3389/fncel.2018.00238
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发表时间：
2018
影响因子：
5.3
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Li N;Cui L;Song G;Guo L;Gu H;Cao H;Li GD;Zhou Y
DISC 1基因是一个与精神分裂症、双相情感障碍和重性抑郁症等神经精神疾病密切相关的候选易感基因，这些疾病都是由基因突变和环境危险因素（如流感、创伤和压力）相互作用的结果。青春期是易受压力和压力相关精神疾病影响的关键时期。在之前的研究中，我们发现尽管DISC 1 L100 P点突变小鼠表现出物体识别缺陷，但它们的社交能力和社交记忆相对正常。因此，本研究旨在探讨青少年压力与DISC 1 L100 P基因点突变之间的交互作用是否影响成年人的社会记忆，并探讨其可能的机制。我们发现，青春期的压力（隔离从5周龄至8周龄）专门损害成年DISC 1 L100 P小鼠的社会记忆，但不是WT同窝出生的，这可以通过非典型抗精神病药物氯氮平的管理挽救。另一方面，它不会引起成年小鼠的焦虑或抑郁。青春期隔离加剧了DISC 1 L100 P小鼠海马中的成年神经发生缺陷，而对WT小鼠没有影响。此外，我们发现，青少年隔离导致海马回路中突触传递和可塑性的长期持续变化，其中一些是DISC 1 L100 P小鼠特有的。总之，我们在这里确定了基因突变（DISC 1 L100 P）和青少年社会压力之间的特定相互作用，损害成年海马回路中的突触功能和社会记忆。亮点-青春期隔离（5周至8周龄）与DISC 1 L100 P点突变结合时损害成年社会记忆。-青春期隔离加剧L100 P小鼠海马中的成年神经发生缺陷，但对WT小鼠没有类似的影响。-青春期隔离导致DISC 1 L100 P小鼠海马网络的突触传递和可塑性发生长期持续的变化。
Disrupted-in-schizophrenia 1 (DISC1) is a strong candidate susceptibility gene for a spectrum of neuropsychiatric diseases including schizophrenia, bipolar disorder and major depression, all of which are thought to result from interactions between gene mutations and environmental risk factors such as influenza, trauma and stress. Adolescence is a key period susceptible to stress and stress-related mental illnesses. In a previous study, we found that although DISC1 L100P point mutation mice shows object recognition deficits, their sociability and social memory are relatively normal. Therefore, in this article, we investigated whether the interaction between adolescent stress and DISC1 L100P point mutation affects adult social memory, and we explored the underlying mechanisms. We found that adolescent stress (isolation from 5 weeks to 8 weeks of age) specifically impaired social memory of adult DISC1 L100P mice but not that of WT littermates, which could be rescued by administration of atypical antipsychotic drug clozapine. On the other hand, it did not induce anxiety or depression in adult mice. Adolescent isolation exacerbated adult neurogenesis deficits in the hippocampus of DISC1 L100P mice, while it had no effect on WT mice. In addition, we found that adolescent isolation led to long lasting changes in synaptic transmission and plasticity in the hippocampal circuits, some of which are specific for DISC1 L100P mice. In summary, we identified here the specific interaction between genetic mutation (DISC1 L100P) and adolescence social stress that damages synaptic function and social memory in adult hippocampal circuits. Highlights – Adolescent isolation (from 5 weeks to 8 weeks of age) impairs adult social memory when combined with DISC1 L100P point mutation.– Adolescent isolation exacerbates adult neurogenesis deficit in the hippocampus of L100P mice but has no similar effect on WT mice.– Adolescent isolation causes long lasting changes in synaptic transmission and plasticity of the hippocampal network in DISC1 L100P mice.
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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
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
影响因子：
3.6
作者：
Cui L;Sun W;Yu M;Li N;Guo L;Gu H;Zhou Y
通讯作者：
Zhou Y
影响因子：
10.6
作者：
Abazyan, Bagrat;Nomura, Jun;Kannan, Geetha;Ishizuka, Koko;Tamashiro, Kellie L.;Nucifora, Frederick;Pogorelov, Vladimir;Ladenheim, Bruce;Yang, Chunxia;Krasnova, Irina N.;Cadet, Jean Lud;Pardo, Carlos;Mori, Susumu;Kamiya, Atsushi;Vogel, Michael W.;Sawa, Akira;Ross, Christopher A.;Pletnikov, Mikhail V.
通讯作者：
Pletnikov, Mikhail V.
影响因子：
14.8
作者：
Kee, Nohjin;Teixeira, Catia M.;Frankland, Paul W.
通讯作者：
Frankland, Paul W.
影响因子：
3.4
作者：
Harrison, PJ
通讯作者：
Harrison, PJ