Abnormalities in astrocytes occur in the brains of patients with Tuberous Sclerosis Complex (TSC) and may contribute to the pathogenesis of neurological dysfunction in this disease. Here, we report that knock-out mice with Tsc1 gene inactivation in glia (Tsc1GFAPCKO mice) exhibit decreased expression of the astrocytic connexin protein, Cx43, and an associated impairment in gap junction coupling between astrocytes. Correspondingly, hippocampal slices from Tsc1GFAPCKO mice have increased extracellular potassium concentration in response to stimulation. This impaired potassium buffering can be attributed to abnormal gap junction coupling, as a gap junction inhibitor elicits an additional increase in potassium concentration in control, but not Tsc1GFAPCKO slices. Furthermore, treatment with a mammalian target of rapamycin inhibitor reverses the deficient Cx43 expression and impaired potassium buffering. These findings suggest that Tsc1 inactivation in astrocytes causes defects in astrocytic gap junction coupling and potassium clearance, which may contribute to epilepsy in Tsc1GFAPCKO mice.
|Number of pages||9|
|Journal||Neurobiology of Disease|
|State||Published - May 2009|
- Tuberous sclerosis