Impaired glutamate recycling and GluN2B‐mediated neuronal calcium overload in mice lacking TGF‐β1 in the CNS

摘要: 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 not well understood. We generated CNS-specific TGF-β1-deficient mouse model investigate functional consequences of TGF-β1-deficiency in adult brain. found depletion CNS resulted loss astrocyte glutamate transporter (GluT) proteins GLT-1 (EAAT2) and GLAST (EAAT1) decreased uptake hippocampus. Treatment with induced expression cultured astrocytes enhanced astroglial uptake. Similar GLT-1-deficient mice, CNS-TGF-β1-deficient mice had reduced brain weight CA1 hippocampal region. showed GluN2B-dependent aberrant synaptic plasticity area hippocampus similar transport inhibitor DL-TBOA these were highly sensitive excitotoxic injury. In addition, neurons from elevated GluN2B-mediated calcium signals response extrasynaptic receptor stimulation, whereas cells treated exhibited signals. summary, our study demonstrates previously unrecognized function control extracellular homeostasis responses