Dysbindin-1, BDNF, and GABAergic Transmission in Schizophrenia.
Dysbindin-1, BDNF, and GABAergic Transmission in Schizophrenia.
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DOI：
10.3389/fpsyt.2022.876749
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发表时间：
2022
影响因子：
4.7
通讯作者：
Lin, Da-Ting
中科院分区：
文献类型：
--
作者：
Jun, Rachel;Zhang, Wen;Beacher, Nicholas J.;Zhang, Yan;Li, Yun;Lin, Da-Ting
关键词：
精神分裂症是一种以幻觉、快感缺失、思维障碍和认知障碍为特征的精神障碍。遗传和环境因素都会导致精神分裂症。异常结合蛋白1(DTNBP1)和脑源性神经营养因子(BDNF)都是精神分裂症的遗传因素。缺乏Dtnbp1的小鼠表现出类似于人类精神分裂症患者的行为缺陷。DTNBP1在突触形成和维持、受体转运和神经递质释放中发挥重要作用。DTNBP1与其他7种蛋白质共同组装成一个大的蛋白质复合体，称为溶酶体相关细胞器复合体的生物发生-1(BLOC-1)。大致密核小泡(LDCV)参与激素和神经肽的分泌，包括BDNF。脑源性神经营养因子在神经元发育、存活和突触可塑性中发挥重要作用。脑源性神经营养因子在维持脑内GABA能抑制传递中也起着关键作用。两项独立的研究表明，DTNBP1介导活性依赖的BDNF分泌，以维持抑制性传递。兴奋性和抑制性神经活动的失衡被认为是精神分裂症的原因之一。在这篇简短的综述中，我们将讨论精神分裂症的潜在致病机制，涉及DTNBP1、BDNF和抑制性传递。我们还将讨论这些过程是如何相互关联的，并与精神分裂症发展的更高风险相关联。
Schizophrenia is a psychiatric disorder characterized by hallucinations, anhedonia, disordered thinking, and cognitive impairments. Both genetic and environmental factors contribute to schizophrenia. Dysbindin-1 (DTNBP1) and brain-derived neurotrophic factor (BDNF) are both genetic factors associated with schizophrenia. Mice lacking Dtnbp1 showed behavioral deficits similar to human patients suffering from schizophrenia. DTNBP1 plays important functions in synapse formation and maintenance, receptor trafficking, and neurotransmitter release. DTNBP1 is co-assembled with 7 other proteins into a large protein complex, known as the biogenesis of lysosome-related organelles complex-1 (BLOC-1). Large dense-core vesicles (LDCVs) are involved in the secretion of hormones and neuropeptides, including BDNF. BDNF plays important roles in neuronal development, survival, and synaptic plasticity. BDNF is also critical in maintaining GABAergic inhibitory transmission in the brain. Two studies independently showed that DTNBP1 mediated activity-dependent BDNF secretion to maintain inhibitory transmission. Imbalance of excitatory and inhibitory neural activities is thought to contribute to schizophrenia. In this mini-review, we will discuss a potential pathogenetic mechanism for schizophrenia involving DTNBP1, BDNF, and inhibitory transmission. We will also discuss how these processes are interrelated and associated with a higher risk of schizophrenia development.
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DOI：
10.1111/j.1601-183x.2009.00477.x
发表时间：
2009-06
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Cox MM;Tucker AM;Tang J;Talbot K;Richer DC;Yeh L;Arnold SE
通讯作者：
Arnold SE
影响因子：
5.4
作者：
Al-Shammari AR;Bhardwaj SK;Musaelyan K;Srivastava LK;Szele FG
通讯作者：
Szele FG
DOI：
10.1126/science.1179685
发表时间：
2009-11-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dickman DK;Davis GW
通讯作者：
Davis GW
影响因子：
34.7
作者：
Ascoli, Giorgio A.;Alonso-Nanclares, Lidia;Anderson, Stewart A.;Barrionuevo, German;Benavides-Piccione, Ruth;Burkhalter, Andreas;Buzsaki, Gyoergy;Cauli, Bruno;DeFelipe, Javier;Fairen, Alfonso;Feldmeyer, Dirk;Fishell, Gord;Fregnac, Yves;Freund, Tamas F.;Gardner, Daniel;Gardner, Esther P.;Goldberg, Jesse H.;Helmstaedter, Moritz;Hestrin, Shaul;Karube, Fuyuki;Kisvarday, Zoltan F.;Lambolez, Bertrand;Lewis, David A.;Marin, Oscar;Markram, Henry;Munoz, Alberto;Packer, Adam;Petersen, Carl C. H.;Rockland, Kathleen S.;Rossier, Jean;Rudy, Bernardo;Somogyi, Peter;Staiger, Jochen F.;Tamas, Gabor;Thomson, Alex M.;Toledo-Rodriguez, Maria;Wang, Yun;West, David C.;Yuste, Rafael
通讯作者：
Yuste, Rafael
影响因子：
8.2
作者：
Balu, Darrick T.;Coyle, Joseph T.
通讯作者：
Coyle, Joseph T.