Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model

• DOI: 10.1002/ana.10648
• Publication Date: 2003-07-28T11:14:16Z
• Authors: Michael Wong; Kevin C. Ess; Erik J. Uhlmann; Laura A. Jansen; Wen Li; Peter B. Crino; Steven Mennerick; Kelvin A. Yamada; David H. Gutmann
• Keywords: Mice, Knockout; Epilepsy; Tumor Suppressor Proteins; Blotting, Western; Biological Transport, Active; Glutamic Acid; Proteins; Tuberous Sclerosis Complex 1 Protein; Electrophysiology; Mice; 03 medical and health sciences; 0302 clinical medicine; Tuberous Sclerosis; Astrocytes; Synapses; Animals; Homeostasis; Gliosis; RNA, Messenger; Neuroglia; Cells, Cultured

AbstractExcessive astrocytosis in cortical tubers in tuberous sclerosis complex (TSC) suggests that astrocytes may be important for epileptogenesis in TSC. We previously demonstrated that astrocyte‐specificTsc1gene inactivation in mice (Tsc1cKO mice) results in progressive epilepsy. Here, we report that glutamate transporter expression and function is impaired inTsc1cKO astrocytes.Tsc1cKO mice exhibit decreased GLT‐1 and GLAST protein expression. Electrophysiological assays demonstrate a functional decrease in glutamate transport currents ofTsc1cKO astrocytes in hippocampal slices and astrocyte cultures. These findings suggest thatTsc1inactivation in astrocytes causes dysfunctional glutamate homeostasis, leading to seizure development in TSC. Ann Neurol 2003