Artikel ; Online: A role of dentate gyrus mechanistic target of rapamycin activation in epileptogenesis in a mouse model of posttraumatic epilepsy.
2024
Abstract: Objective: The mechanistic target of rapamycin (mTOR) pathway has been implicated in promoting epileptogenesis in animal models of acquired epilepsy, such as posttraumatic epilepsy (PTE) following traumatic brain injury (TBI). However, the specific ... ...
Abstract | Objective: The mechanistic target of rapamycin (mTOR) pathway has been implicated in promoting epileptogenesis in animal models of acquired epilepsy, such as posttraumatic epilepsy (PTE) following traumatic brain injury (TBI). However, the specific anatomical regions and neuronal populations mediating mTOR's role in epileptogenesis are not well defined. In this study, we tested the hypothesis that mTOR activation in dentate gyrus granule cells promotes neuronal death, mossy fiber sprouting, and PTE in the controlled cortical impact (CCI) model of TBI. Methods: An adeno-associated virus (AAV)-Cre viral vector was injected into the hippocampus of Rptor Results: AAV-Cre injection primarily affected the dentate gyrus and inhibited hippocampal mTOR activation following CCI injury. AAV-Cre-injected mice had reduced neuronal death in dentate gyrus detected by Fluoro-Jade B staining and decreased mossy fiber sprouting by ZnT3 immunostaining. Finally, AAV-Cre-injected mice exhibited a decrease in incidence of PTE. Significance: mTOR pathway activation in dentate gyrus granule cells may at least partly mediate pathological abnormalities and epileptogenesis in models of TBI and PTE. Targeted modulation of mTOR activity in this hippocampal network may represent a focused therapeutic approach for antiepileptogenesis and prevention of PTE. |
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Sprache | Englisch |
Erscheinungsdatum | 2024-05-18 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article |
ZDB-ID | 216382-2 |
ISSN | 1528-1167 ; 0013-9580 |
ISSN (online) | 1528-1167 |
ISSN | 0013-9580 |
DOI | 10.1111/epi.18011 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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