| First Author | Koeglsperger T | Year | 2013 |
| Journal | Glia | Volume | 61 |
| Issue | 6 | Pages | 985-1002 |
| PubMed ID | 23536313 | Mgi Jnum | J:195270 |
| Mgi Id | MGI:5477840 | Doi | 10.1002/glia.22490 |
| Citation | Koeglsperger T, et al. (2013) Impaired glutamate recycling and GluN2B-mediated neuronal calcium overload in mice lacking TGF-beta1 in the CNS. Glia 61(6):985-1002 |
| abstractText | Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine expressed throughout the CNS. Previous studies demonstrated that TGF-beta1 contributes to maintain neuronal survival, but mechanistically this effect is not well understood. We generated a CNS-specific TGF-beta1-deficient mouse model to investigate the functional consequences of TGF-beta1-deficiency in the adult mouse brain. We found that depletion of TGF-beta1 in the CNS resulted in a loss of the astrocyte glutamate transporter (GluT) proteins GLT-1 (EAAT2) and GLAST (EAAT1) and decreased glutamate uptake in the mouse hippocampus. Treatment with TGF-beta1 induced the expression of GLAST and GLT-1 in cultured astrocytes and enhanced astroglial glutamate uptake. Similar to GLT-1-deficient mice, CNS-TGF-beta1-deficient mice had reduced brain weight and neuronal loss in the CA1 hippocampal region. CNS-TGF-beta1-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-beta1-deficient mice had elevated GluN2B-mediated calcium signals in response to extrasynaptic glutamate receptor stimulation, whereas cells treated with TGF-beta1 exhibited reduced GluN2B-mediated calcium signals. In summary, our study demonstrates a previously unrecognized function of TGF-beta1 in the CNS to control extracellular glutamate homeostasis and GluN2B-mediated calcium responses in the mouse hippocampus. |
