Abstract | BACKGROUND: METHODS: At postnatal day P12, developmental status epilepticus (DSE) was induced in male Tsc2+/- (Eker) and wild-type rats, establishing four experimental groups including controls. In adult animals (n = 36), the behavior was assessed in the paradigms of social interaction test, elevated plus-maze, light-dark test, Y-maze, and novel object recognition. The testing was carried out before medication (T1), during a 2-week treatment with the mTOR inhibitor everolimus (T2) and after an 8-week washing-out (T3). Electroencephalographic (EEG) activity was recorded in a separate set of animals (n = 18). RESULTS: Both Tsc2+/- mutation and DSE caused social behavior deficits and epileptiform EEG abnormalities (T1). Everolimus led to a persistent improvement of the social deficit induced by Tsc2+/-, while deficits related to DSE did not respond to everolimus (T2, T3). CONCLUSIONS: These findings may contribute to an explanation why ASD symptoms in individuals with TSC, where comorbid early-onset epilepsy is common, were not reliably ameliorated by mTOR inhibitors in clinical studies.
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Authors | Tomas Petrasek, Iveta Vojtechova, Ondrej Klovrza, Klara Tuckova, Cestmir Vejmola, Jakub Rak, Anna Sulakova, Daniel Kaping, Nadine Bernhardt, Petrus J de Vries, Jakub Otahal, Robert Waltereit |
Journal | Journal of neurodevelopmental disorders
(J Neurodev Disord)
Vol. 13
Issue 1
Pg. 14
(04 17 2021)
ISSN: 1866-1955 [Electronic] England |
PMID | 33863288
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Tsc2 protein, rat
- Tuberous Sclerosis Complex 2 Protein
- mTOR protein, rat
- TOR Serine-Threonine Kinases
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Topics |
- Animals
- Autistic Disorder
- Haploinsufficiency
- Male
- Rats
- Status Epilepticus
- TOR Serine-Threonine Kinases
(genetics)
- Tuberous Sclerosis Complex 2 Protein
(genetics)
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