Mutant disrupted-in-schizophrenia 1 in astrocytes: focus on glutamate metabolism.
Mutant disrupted-in-schizophrenia 1 in astrocytes: focus on glutamate metabolism.
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DOI：
10.1002/jnr.23459
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发表时间：
2014-12
影响因子：
4.2
通讯作者：
Pletnikov, Mikhail
中科院分区：
文献类型：
--
作者：
Abazyan, Sofya;Yang, Eun Ju;Abazyan, Bagrat;Xia, Meng;Yang, Chunxia;Rojas, Camilo;Slusher, Barbara;Sattler, Rita;Pletnikov, Mikhail
精神分裂症1（DISC 1）是一种遗传风险因素，与主要精神障碍有关。DISC 1结合并稳定丝氨酸消旋酶（SR），以调节星形胶质细胞产生D-丝氨酸，促进谷氨酸（GLU）神经传递。然而，星形胶质细胞DISC 1可能参与GLU的合成、代谢、再吸收或分泌仍有待探讨。因此，我们研究了显性负突变DISC 1对GLU代谢的各个方面的影响，使用原代星形胶质细胞培养物和来自星形胶质细胞限制性表达突变DISC 1的转基因小鼠的海马组织。虽然突变DISC 1对星形胶质细胞增殖、GLU再摄取、谷氨酰胺酶或谷氨酸羧肽酶II活性没有显著影响，但突变DISC 1的表达与丙氨酸-丝氨酸-半胱氨酸转运蛋白2的水平增加相关，初级星形胶质细胞和海马中的囊泡谷氨酸转运体1和3以及NMDA的NR 1亚基表达升高和NR 2A亚基表达降低在出生后第21天海马体中的受体。我们的研究结果表明，减少D-丝氨酸生产星形胶质细胞突变DISC 1可能会导致代偿性变化的氨基酸转运蛋白和NMDA受体的水平在三方突触的背景下。
Disrupted-In-Schizophrenia 1 (DISC1) is a genetic risk factor that has been implicated in major mental disorders. DISC1 binds to and stabilizes serine racemase (SR) to regulate production of D-serine by astrocytes, contributing to glutamate (GLU) neurotransmission. However, the possible involvement of astrocytic DISC1 in synthesis, metabolism, re-uptake or secretion of GLU remains unexplored. Thus, we studied the effects of dominant-negative mutant DISC1 on various aspects of GLU metabolism using primary astrocyte cultures and the hippocampal tissue from transgenic mice with astrocyte-restricted expression of mutant DISC1. While mutant DISC1 had no significant effects on astrocyte proliferation, GLU re-uptake, Glutaminase or Glutamate carboxypeptidase II activity, expression of mutant DISC1 was associated with increased levels of alanine-serine-cysteine transporter 2, vesicular glutamate transporters 1 and 3 in primary astrocytes and in the hippocampus as well as elevated expression of the NR1 subunit and diminished expression of the NR2A subunit of NMDA receptors in the hippocampus at postnatal day 21. Our findings indicate that decreased D-serine production by astrocytic mutant DISC1 may lead to compensatory changes in levels of the amino acid transporters and NMDA receptors in the context of tripartite synapse.
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影响因子：
34.7
作者：
Clarke, Laura E.;Barres, Ben A.
通讯作者：
Barres, Ben A.
影响因子：
5.3
作者：
Montana, V;Ni, YC;Parpura, V
通讯作者：
Parpura, V
DOI：
10.1016/j.lpm.2011.01.031
发表时间：
2012-01-01
期刊：
Presse medicale (Paris, France : 1983)
影响因子：
--
作者：
Naar, Fabien;Dinh, Aurelien;Bernard, Louis
通讯作者：
Bernard, Louis
影响因子：
4.5
作者：
Eastwood, SL;Harrison, PJ
通讯作者：
Harrison, PJ
DOI：
10.1016/j.pnpbp.2008.10.005
发表时间：
2009-02-01
影响因子：
5.6
作者：
Feyissa, Anteneh M.;Chandran, Agata;Stockmeier, Craig A.;Karolewicz, Beata
通讯作者：
Karolewicz, Beata