Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex
Astrocyte dysfunction may contribute to epileptogenesis and other neurological deficits in Tuberous Sclerosis Complex (TSC). In particular, decreased expression and function of astrocyte glutamate transporters have been implicated in causing elevated extracellular glutamate levels, neuronal death, a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109003751 |
| _version_ | 1818616222571298816 |
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| author | Ling-Hui Zeng Adam W. Bero Bo Zhang David M. Holtzman Michael Wong |
| author_facet | Ling-Hui Zeng Adam W. Bero Bo Zhang David M. Holtzman Michael Wong |
| author_sort | Ling-Hui Zeng |
| collection | DOAJ |
| description | Astrocyte dysfunction may contribute to epileptogenesis and other neurological deficits in Tuberous Sclerosis Complex (TSC). In particular, decreased expression and function of astrocyte glutamate transporters have been implicated in causing elevated extracellular glutamate levels, neuronal death, and epilepsy in a mouse model of TSC (Tsc1GFAPCKO mice), involving inactivation of the Tsc1 gene primarily in astrocytes. Here, we tested whether pharmacological induction of astrocyte glutamate transporter expression can prevent the neurological phenotype of Tsc1GFAPCKO mice. Early treatment with ceftriaxone prior to the onset of epilepsy increased expression of astrocyte glutamate transporters, decreased extracellular glutamate levels, neuronal death, and seizure frequency, and improved survival in Tsc1GFAPCKO mice. In contrast, late treatment with ceftriaxone after onset of epilepsy increased glutamate transporter expression, but had no effect on seizures. These results indicate that astrocyte glutamate transporters contribute to epileptogenesis in Tsc1GFAPCKO mice and suggest novel therapeutic strategies for epilepsy in TSC directed at astrocytes. |
| first_indexed | 2024-12-16T16:46:22Z |
| format | Article |
| id | doaj.art-d8f4d316b009473e83ea0e5f23b98b5b |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T16:46:22Z |
| publishDate | 2010-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d8f4d316b009473e83ea0e5f23b98b5b2022-12-21T22:24:11ZengElsevierNeurobiology of Disease1095-953X2010-03-01373764771Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis ComplexLing-Hui Zeng0Adam W. Bero1Bo Zhang2David M. Holtzman3Michael Wong4Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author. Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Fax: +1 314 362 9462.Astrocyte dysfunction may contribute to epileptogenesis and other neurological deficits in Tuberous Sclerosis Complex (TSC). In particular, decreased expression and function of astrocyte glutamate transporters have been implicated in causing elevated extracellular glutamate levels, neuronal death, and epilepsy in a mouse model of TSC (Tsc1GFAPCKO mice), involving inactivation of the Tsc1 gene primarily in astrocytes. Here, we tested whether pharmacological induction of astrocyte glutamate transporter expression can prevent the neurological phenotype of Tsc1GFAPCKO mice. Early treatment with ceftriaxone prior to the onset of epilepsy increased expression of astrocyte glutamate transporters, decreased extracellular glutamate levels, neuronal death, and seizure frequency, and improved survival in Tsc1GFAPCKO mice. In contrast, late treatment with ceftriaxone after onset of epilepsy increased glutamate transporter expression, but had no effect on seizures. These results indicate that astrocyte glutamate transporters contribute to epileptogenesis in Tsc1GFAPCKO mice and suggest novel therapeutic strategies for epilepsy in TSC directed at astrocytes.http://www.sciencedirect.com/science/article/pii/S0969996109003751EpilepsySeizureGliaGLT-1CeftriaxoneEpileptogenesis |
| spellingShingle | Ling-Hui Zeng Adam W. Bero Bo Zhang David M. Holtzman Michael Wong Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex Neurobiology of Disease Epilepsy Seizure Glia GLT-1 Ceftriaxone Epileptogenesis |
| title | Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex |
| title_full | Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex |
| title_fullStr | Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex |
| title_full_unstemmed | Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex |
| title_short | Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of Tuberous Sclerosis Complex |
| title_sort | modulation of astrocyte glutamate transporters decreases seizures in a mouse model of tuberous sclerosis complex |
| topic | Epilepsy Seizure Glia GLT-1 Ceftriaxone Epileptogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109003751 |
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