The mTOR signaling pathway and neuronal stem/progenitor cell proliferation in the hippocampus are altered during the development of absence epilepsy in a genetic animal model.

Abstract

Hyperactivation of mammalian target of rapamycin (mTOR) signaling pathway occurs after an epileptogenic insult and, its inhibition prevents the development of spontaneous seizures. We have recently demonstrated that mTOR's inhibition by rapamycin (started before seizure onset), permanently reduces the development of spontaneous absence seizures in WAG/Rij rats, an animal model of absence epilepsy; furthermore, mTOR phosphorylation was increased in adult WAG/Rij rats' cortex, but not other brain areas. However, it was not clear whether this hyperphosphorylation was a cause or a consequence of absence seizure. Here, we have addressed this issue by analyzing immunohistochemically: (1) the brain levels of total and phosphorylated mTOR in young (before seizures) and adult WAG/Rij rats; (2) the proliferation of hippocampal neuronal stem/progenitor cells assessed by BrdU analysis at different ages. WAG/Rij rats have higher levels of total mTOR in several brain areas than Wistar rats; phospho-mTOR staining is higher in young WAG/Rij rats than control and adult WAG/Rij rats. Finally, the age-related decline in hippocampal neural progenitor cell proliferation rate was slower in WAG/Rij than Wistar rats. Our results support a role for persistent mTOR activation and consequent change in hippocampal progenitor cell proliferation during the epileptogenic process leading to the development of absence seizures in WAG/Rij rats.

• Authors: Emilio Russo, Paolo Follesa, Rita Citraro, Caterina Camastra, Annalidia Donato, Daniela Isola, Andrew Constanti, Giovambattista De Sarro, Giuseppe Donato
• Journal: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (Neurol Sci) Vol. 35 Issue 11 Pg. 1793-9 (Nov 2014) ISSN: 1590-3478 [Electronic] Italy
• PMID: 24889758 (Publication Type: Journal Article)

Chemical References

• mTOR protein, rat
• TOR Serine-Threonine Kinases

Topics

• Animals
• Cell Proliferation (physiology)
• Disease Models, Animal
• Electroencephalography
• Epilepsy, Absence (metabolism, pathology, physiopathology)
• Hippocampus (metabolism, pathology)
• Immunohistochemistry
• Male
• Neural Stem Cells (pathology)
• Rats
• Rats, Wistar
• Signal Transduction (physiology)
• TOR Serine-Threonine Kinases (metabolism)