Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex

Zeng LH, Xu L, Gutmann DH, Wong M · 2008 · Annals of Neurology · Atlas ID ZEN2008

What this study shows

Mice lacking Tsc1 mainly in glial cells (Tsc1 GFAP conditional knockout) develop glial overgrowth, progressive epilepsy and early death. Rapamycin started at postnatal day 14, before symptoms, prevented epilepsy and premature death; started at 6 weeks, after seizures had begun, it suppressed seizures and prolonged survival. In the brain, rapamycin reversed the abnormal mTOR pathway activation (measured as phospho-S6), the astrogliosis and the neuronal disorganisation, and increased brain size, compared with vehicle-treated knockouts. The study provided evidence in mice that mTOR inhibition can act on epilepsy itself in TSC, not only on tumours, and it is part of the rationale for the later EXIST-3 seizure trial in patients. Boundary: mouse model with Tsc1 deleted mainly in glia, not the human germline mutation; seizure and survival outcomes in mice only; abstract does not state dose or schedule.

Abstract

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Tuberous sclerosis complex (TSC) represents one of the most common genetic causes of epilepsy. TSC gene inactivation leads to hyperactivation of the mammalian target of rapamycin signaling pathway, raising the intriguing possibility that mammalian target of rapamycin inhibitors might be effective in preventing or treating epilepsy in patients with TSC. Mice with conditional inactivation of the Tsc1 gene primarily in glia (Tsc1(GFAP)CKO mice) develop glial proliferation, progressive epilepsy, and premature death.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mice: Tsc1(GFAP) conditional knockout (Tsc1 deleted mainly in glia) and littermate controls; rapamycin or vehicle from P14 (early) or 6 weeks (late); video-EEG, survival, histology, Western blot for phospho-S6); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mice: Tsc1(GFAP) conditional knockout (Tsc1 deleted mainly in glia) and littermate controls; rapamycin or vehicle from P14 (early) or 6 weeks (late); video-EEG, survival, histology, Western blot for phospho-S6
Journal	Annals of Neurology
Year	2008
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1002/ana.21331 · PMID 18389497 · Free full text (PMC3937593)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Rapamycin vs vehicle, early (from P14) or late (from 6 weeks)
Target	mTORC1
Model	Mouse
Effect	Prevented (early) or suppressed (late) epilepsy and prolonged survival; reduced phospho-S6, astrogliosis, neuronal disorganisation

In the Atlas

Links in the pathway map

Supports TSC1/TSC2 inhibits mTORC1

Cite this paper

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Zeng, L. H., Xu, L., Gutmann, D. H., & Wong, M. (2008). Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Annals of Neurology. https://doi.org/10.1002/ana.21331

@article{ZEN2008,
  author       = {Zeng, L. H. and Xu, L. and Gutmann, D. H. and Wong, M.},
  title        = {{Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex}},
  journal      = {Annals of Neurology},
  year         = {2008},
  doi          = {10.1002/ana.21331},
  note         = {PMID: 18389497},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record ZEN2008) [Data set]. https://mtor-atlas.org/study/ZEN2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ZEN2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ZEN2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ZEN2008/},
  doi          = {10.5281/zenodo.22059963}
}

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