Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model

Michael Wong, Kevin C. Ess, Erik J. Uhlmann, Laura A. Jansen, Wen Li, Peter B. Crino, Steven Mennerick, Kelvin A. Yamada, David H. Gutmann

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

Excessive astrocytosis in cortical tubers in tuberous sclerosis complex (TSC) suggests that astrocytes may be important for epileptogenesis in TSC. We previously demonstrated that astrocyte-specific Tsc1 gene inactivation in mice (Tsc1 cKO mice) results in progressive epilepsy. Here, we report that glutamate transporter expression and function is impaired in Tsc1 cKO astrocytes. Tsc1 cKO mice exhibit decreased GLT-1 and GLAST protein expression. Electrophysiological assays demonstrate a functional decrease in glutamate transport currents of Tsc1 cKO astrocytes in hippocampal slices and astrocyte cultures. These findings suggest that Tsc1 inactivation in astrocytes causes dysfunctional glutamate homeostasis, leading to seizure development in TSC.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
JournalAnnals of neurology
Volume54
Issue number2
DOIs
StatePublished - Aug 1 2003

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