期刊
NEUROBIOLOGY OF DISEASE
卷 34, 期 2, 页码 291-299出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.01.010
关键词
Tuberous sclerosis; Epilepsy; Seizures; Astrocyte; Glia; Connexin; Potassium
资金
- National Institutes of Health (NIH) [K02 NS045583, R01 NS056872]
- Tuberous Sclerosis Alliance
- NIH Neuroscience Blueprint Center [P30 NS057105]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [K02NS045583, P30NS057105, R01NS056872] Funding Source: NIH RePORTER
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 (Tsc1(GFAP)CKO mice) exhibit decreased expression of the astrocytic connexin protein, Cx43, and an associated impairment in gap junction coupling between astrocytes. Correspondingly, hippocampal slices from Tsc1(GFAP)CKO 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 Tsc1(GFAP)CKO 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 Tsc1(GFAP)CKO mice. (C) 2009 Elsevier Inc. All rights reserved.
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