Transgenic overexpression of the type I isoform of neuregulin 1 affects working memory and hippocampal oscillations but not long-term potentiation.
Transgenic overexpression of the type I isoform of neuregulin 1 affects working memory and hippocampal oscillations but not long-term potentiation.
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DOI：
10.1093/cercor/bhr223
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Harrison PJ
中科院分区：
文献类型：
--
作者：
Deakin IH;Nissen W;Law AJ;Lane T;Kanso R;Schwab MH;Nave KA;Lamsa KP;Paulsen O;Bannerman DM;Harrison PJ
神经调节蛋白1（NRG 1）是一种参与神经发育和可塑性的生长因子。它是精神分裂症的候选基因，并且NRG 1 I型亚型的海马表达在该病症中增加。我们研究了过表达NRG 1 I型（NRG 1 tg-I型）的转基因小鼠及其野生型同窝仔，并测量了海马电生理和行为表型。年轻的NRG 1 tg-I型小鼠表现出正常的记忆性能，但在老年NRG 1 tg-I型小鼠，海马依赖性空间工作记忆选择性受损。NRG 1 tg-I型小鼠的海马切片制备物显示卡巴胆碱诱导的γ振荡频率降低，癫痫样活动倾向增加。NRG 1 tg-I型小鼠的长时程增强是正常的。这些结果提供了证据表明，NRG 1 I型影响海马功能和电路。这种作用可能是通过抑制性中间神经元介导的，可能与NRG 1参与精神分裂症有关。然而，这些研究结果与NRG 1的其他遗传和药理学操作相一致，强调了该基因的复杂性和多效性，即使是关于单一亚型。
Neuregulin 1 (NRG1) is a growth factor involved in neurodevelopment and plasticity. It is a schizophrenia candidate gene, and hippocampal expression of the NRG1 type I isoform is increased in the disorder. We have studied transgenic mice overexpressing NRG1 type I (NRG1tg-type I) and their wild-type littermates and measured hippocampal electrophysiological and behavioral phenotypes. Young NRG1tg-type I mice showed normal memory performance, but in older NRG1tg-type I mice, hippocampus-dependent spatial working memory was selectively impaired. Hippocampal slice preparations from NRG1tg-type I mice exhibited a reduced frequency of carbachol-induced gamma oscillations and an increased tendency to epileptiform activity. Long-term potentiation in NRG1tg-type I mice was normal. The results provide evidence that NRG1 type I impacts on hippocampal function and circuitry. The effects are likely mediated via inhibitory interneurons and may be relevant to the involvement of NRG1 in schizophrenia. However, the findings, in concert with those from other genetic and pharmacological manipulations of NRG1, emphasize the complex and pleiotropic nature of the gene, even with regard to a single isoform.
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DOI：
10.1523/jneurosci.1815-08.2008
发表时间：
2008-07-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen YJ;Johnson MA;Lieberman MD;Goodchild RE;Schobel S;Lewandowski N;Rosoklija G;Liu RC;Gingrich JA;Small S;Moore H;Dwork AJ;Talmage DA;Role LW
通讯作者：
Role LW
影响因子：
16.2
作者：
Brinkmann, Bastian G.;Agarwal, Amit;Sereda, Michael W.;Garratt, Alistair N.;Mueller, Thomas;Wende, Hagen;Stassart, Ruth M.;Nawaz, Schanila;Humml, Christian;Velanac, Viktorija;Radyushkin, Konstantin;Goebbels, Sandra;Fischer, Tobias M.;Franklin, Robin J.;Lai, Cary;Ehrenreich, Hannelore;Birchmeier, Carmen;Schwab, Markus H.;Nave, Klaus Armin
通讯作者：
Nave, Klaus Armin
影响因子：
3.8
作者：
Buonanno A
通讯作者：
Buonanno A
DOI：
10.1073/pnas.1010669107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Chen, Yong-Jun;Zhang, Meng;Gao, Tian-Ming
通讯作者：
Gao, Tian-Ming
影响因子：
16.2
作者：
Flames, N;Long, JE;Marín, O
通讯作者：
Marín, O