Investigating the mechanism of antiepileptogenic effect of apigenin in kainate temporal lobe epilepsy: possible role of mTOR

Clarifying the underlying mechanisms of epileptogenesis is important in preventing the progression of chronic epilepsy. In epilepsy, the mTOR (mammalian target of rapamycin) pathway plays a critical role in mediating the mechanism of epileptogenesis. In this study, we investigate whether apigenin ca...

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Bibliographic Details
Published in:Experimental brain research 2023-03, Vol.241 (3), p.753-763
Main Authors: Nikbakht, Farnaz, Hashemi, Paria, Vazifekhah, Somayeh, Babaei, Javad Fahanik
Format: Article
Language:English
Subjects:
Animals
Apigenin - pharmacology
Biomedical and Life Sciences
Biomedicine
Care and treatment
Cell death
Dentate gyrus
Disease Models, Animal
EEG
Epilepsy
Epilepsy, Temporal Lobe
Firing pattern
Health aspects
Hippocampus
Humans
Hyperactivity
Kainic acid
Kainic Acid - pharmacology
Mossy Fibers, Hippocampal
Neurogenesis
Neurology
Neurosciences
Patient outcomes
Rapamycin
Research Article
Seizures
Temporal lobe
Temporal lobe epilepsy
TOR protein
TOR Serine-Threonine Kinases - metabolism
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Summary:Clarifying the underlying mechanisms of epileptogenesis is important in preventing the progression of chronic epilepsy. In epilepsy, the mTOR (mammalian target of rapamycin) pathway plays a critical role in mediating the mechanism of epileptogenesis. In this study, we investigate whether apigenin can exert antiepileptogenic effects through the inhibition of mTOR in the kainate model of epilepsy. For assessing the antiepileptogenic effect of apigenin in kainic acid (KA)-induced temporal lobe epilepsy (TLE) model, apigenin at a dose of 50 mg/kg was administrated by gavage for 6 days. An intracranial electroencephalogram (iEEG) was performed to confirm the establishment of status epilepticus. BrdU was used to detect neurogenesis in the CA3, and dentate gyrus and mossy fiber sproutings were assessed by Timm staining. The expression of mTOR was quantified via western blot. We found that apigenin-pretreatment had a significant inhibitory effect on neural cell death, spontaneous seizure spikes, aberrant neurogenesis, mTOR hyperactivity, and aberrant mossy fiber sprouting. Overall, these results suggest that apigenin has an antiepileptogenic effect and may be a useful target for inhibiting mTOR hyperactivity in epilepsy.
ISSN:0014-4819
1432-1106
DOI:10.1007/s00221-023-06557-1