Impaired glutamate recycling and GluN2B-mediated neuronal calcium overload in mice lacking TGF-β1 in the CNS.
Impaired glutamate recycling and GluN2B-mediated neuronal calcium overload in mice lacking TGF-β1 in the CNS.
复制标题
DOI：
10.1002/glia.22490
复制
发表时间：
2013-06
期刊：
影响因子：
6.2
通讯作者：
Weiner, Howard L.
中科院分区：
文献类型：
--
作者：
Koeglsperger, Thomas;Li, Shaomin;Brenneis, Christian;Saulnier, Jessica L.;Mayo, Lior;Carrier, Yijun;Selkoe, Dennis J.;Weiner, Howard L.
Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine expressed throughout the CNS. Previous studies demonstrated that TGF-β1 contributes to maintain neuronal survival, but mechanistically this effect is not well understood. We generated a CNS-specific TGF-β1-deficient mouse model to investigate the functional consequences of TGF-β1-deficiency in the adult mouse brain. We found that depletion of TGF-β1 in the CNS resulted in a loss of the astrocyte glutamate transporter (GluTs) proteins GLT-1 (EAAT2) and GLAST (EAAT1) and decreased glutamate uptake in the mouse hippocampus. Treatment with TGF-β1 induced the expression of GLAST and GLT-1 in cultured astrocytes and enhanced astroglial glutamate uptake. Similar to GLT-1-deficient mice, CNS-TGF-β1-deficient mice had reduced brain weight and neuronal loss in the CA1 hippocampal region. CNS-TGF-β1-deficient mice showed GluN2B-dependent aberrant synaptic plasticity in the CA1 area of the hippocampus similar to the glutamate transport inhibitor DL-TBOA and these mice were highly sensitive to excitotoxic injury. In addition, hippocampal neurons from TGF-β1-deficient mice had elevated GluN2B-mediated calcium signals in response to extrasynaptic glutamate receptor stimulation, whereas cells treated with TGF-β1 exhibited reduced GluN2B-mediated calcium signals. In summary, our study demonstrates a previously unrecognized function of TGF-β1 in the CNS to control extracellular glutamate homeostasis and GluN2B-mediated calcium responses in the mouse hippocampus.
登录
查看更多内容
影响因子：
3.9
作者：
Hardingham GE
通讯作者：
Hardingham GE
DOI：
10.1097/01.wcb.0000090080.64176.44
发表时间：
2003-10-01
影响因子：
6.3
作者：
Boche, D;Cunningham, C;Perry, VH
通讯作者：
Perry, VH
影响因子：
25
作者：
Arnth-Jensen, N;Jabaudon, D;Scanziani, M
通讯作者：
Scanziani, M
影响因子：
4.4
作者：
Condorelli, DF;DellAlbani, P;Stella, AMG
通讯作者：
Stella, AMG
影响因子：
4.2
作者：
Gegelashvili, G;Dehnes, Y;Schousboe, A
通讯作者：
Schousboe, A