title: Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman.
abstract: Epilepsy in menopausal women presents several challenges in the treatment including an increased risk of seizures due to hormone replacement therapy. We investigated the hypothesis if raloxifene, a selective oestrogen receptor modulator, could be employed to prevent behavioural seizures and morphological alterations in a mouse model mimicking epilepsy in postmenopausal women. Female mice were made ovotoxic by treatment with 4-vinylcyclohexene diepoxide (VCD) to mimic a postmenopausal state. They were then subjected to kainic acid (KA)-induced seizures and neurotoxicity, as assessed by microscopic examination of hippocampus, relevant to human temporal lobe epilepsy. VCD administration (for 15days followed by a drug-free period of 30days) induced ovotoxicity in mice as evidenced by reduced number of primary ovarian follicles. This was accompanied by a 62.4% reduction in serum oestradiol levels. The bone mineral density of ovotoxic mice, however, remained unaffected. Raloxifene (8mg/kg) reduced the seizure severity score in both normal and ovotoxic mice and protected against degeneration induced by KA in the CA3, CA1 sub-fields and hilus of the DG. Hippocampal TGF-β3 levels were not affected by any of the treatments. We show the potential protective role of raloxifene in preventing seizures and neuronal damage in a mouse model mimicking epilepsy in postmenopausal women which was found unrelated to hippocampal TGF-β3. Raloxifene might represent a novel therapeutic option for postmenopausal temporal lobe epileptic woman.
authors.affiliation: Neurobehavioural Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: F H
authors.initials: FH
authors.lastname: Pottoo
authors.affiliation: Neurobehavioural Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: M
authors.initials: M
authors.lastname: Bhowmik
authors.affiliation: Neurobehavioural Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India. Electronic address: divyavohora@hotmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Vohora
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D053138:Cyclohexenes / Q000494:pharmacology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D014753:Vinyl Compounds / Q000494:pharmacology
chemical_list: D053138:Cyclohexenes; D053782:Transforming Growth Factor beta3; D014753:Vinyl Compounds; D020849:Raloxifene Hydrochloride; C012606:4-vinyl-1-cyclohexene dioxide; D007608:Kainic Acid
keywords: Kainic acid; Ovotoxicity; Raloxifene; TGF-β3; VCD