Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model.

Wong M, Ess KC, Uhlmann EJ, Jansen LA, Li W, Crino PB, Mennerick S, Yamada KA, Gutmann DH
Ann Neurol. 2003 54 (2): 251-6

PMID: 12891680 · DOI:10.1002/ana.10648

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.

MeSH Terms (19)

Animals Astrocytes Biological Transport, Active Blotting, Western Cells, Cultured Electrophysiology Epilepsy Gliosis Glutamic Acid Homeostasis Mice Mice, Knockout Neuroglia Proteins RNA, Messenger Synapses Tuberous Sclerosis Tuberous Sclerosis Complex 1 Protein Tumor Suppressor Proteins

Connections (1)

This publication is referenced by other Labnodes entities: