The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits.
The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits.
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DOI：
10.1016/j.brainresbull.2010.07.012
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发表时间：
2010-09-30
影响因子：
3.8
通讯作者：
Buonanno A
中科院分区：
文献类型：
--
作者：
Buonanno A
许多遗传连锁和关联研究暗示神经调节蛋白erbb受体（NRG-ErbB）信号通路的成员是精神分裂症的“危险”基因。本综述的重点是提出由Neuregulin-ErbB信号网络调节的神经生物学机制，该机制可能在精神分裂症中发生改变并有助于其病因学。为此，不同的神经递质通路，神经元亚型和神经网络系统改变在精神分裂症初步讨论。接下来，从NRG1和ErbB4信号通路在调节谷氨酸能、gaba能和多巴胺能神经传递以及调节突触可塑性和γ振荡中的功能作用出发，综述NRG1和ErbB4与精神分裂症相关基因研究的可能意义。研究人员强调了gaba能中间神经元中ErbB4受体表达受限的重要性，特别是它们在小蛋白阳性快速尖峰中间神经元的谷氨酸能突触中的表达，抑制驱动的调节可以解释NRG-ErbB信号传导对γ振荡和锥体神经元输出的巨大影响。一个案例的原因是NRG-ErbB信号通路构成了一个“生物学上合理的”系统，可以理解在发展过程中与精神分裂症相关的复杂的阳性、阴性和认知缺陷的致病机制。
Numerous genetic linkage and association studies implicate members of the Neuregulin-ErbB receptor (NRG-ErbB) signaling pathway as schizophrenia “at risk” genes. An emphasis of this review is to propose plausible neurobiological mechanisms, regulated by the Neuregulin-ErbB signaling network, that may be altered in schizophrenia and contribute to its etiology. To this end, the distinct neurotransmitter pathways, neuronal subtypes and neural network systems altered in schizophrenia are initially discussed. Next, the review focuses on the possible significance of genetic studies associating NRG1 and ErbB4 with schizophrenia, in light of the functional role of this signaling pathway in regulating glutamatergic, GABAergic and dopaminergic neurotransmission, as well as modulating synaptic plasticity and gamma oscillations. The importance of restricted ErbB4 receptor expression in GABAergic interneurons is emphasized, particularly their expression at glutamatergic synapses of parvalbumin-positive fast spiking interneurons where modulation of inhibitory drive could account for the dramatic effects of NRG-ErbB signaling on gamma oscillations and pyramidal neuron output. A case is made for reasons that the NRG-ErbB signaling pathway constitutes a “biologically plausible” system for understanding the pathogenic mechanisms that may underlie the complex array of positive, negative and cognitive deficits associated with schizophrenia during development.
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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：
7.8
作者：
Bao, JX;Wolpowitz, D;Role, LW;Talmage, DA
通讯作者：
Talmage, DA
影响因子：
9.8
作者：
Chen, Pei-Lung;Avramopoulos, Dimitrios;Valle, David
通讯作者：
Valle, David
DOI：
10.1523/jneurosci.0605-10.2010
发表时间：
2010-07-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen Y;Hancock ML;Role LW;Talmage DA
通讯作者：
Talmage DA
影响因子：
5.3
作者：
Corfas, G;Velardez, MO;Peles, E
通讯作者：
Peles, E