The aim of this study was to evaluate the efficacy of three antihormones, tamoxifen (TXF, an antiestrogen), mifepristone (MIF, an antiprogesterone) and cyproterone (CYP, an antiandrogen) in two major models of experimental epilepsy, electrically and pentetrazole (PTZ)-evoked seizures in mice. TXF (20-50 mg/kg) significantly raised the threshold for electroconvulsions in female mice, whereas CYP was active in male mice. Similar effects were observed in castrated mice. Different data were obtained in sexually immature animals since both TXF and CYP exerted anticonvulsive effects in animals of both genders. MIF (5-50 mg/kg) remained without effect on electrically evoked seizures in mice. The anticonvulsive action of TXF was reversed by aminophylline, bicuculline, kainic acid and N-methyl-D-aspartic acid, but not by estradiol or strychnine. The protective action of CYP was reversed by aminophylline and bicuculline, but not by testosterone, kainic acid, N-methyl-D-aspartic acid or strychnine. All three antihormones were ineffective against PTZ-induced convulsions in mice. Our results suggest that the action of TXF and CYP might be indirectly associated with the respective hormonal receptor-mediated events, but the nature of this dependence is unclear and further investigations are needed to elucidate this phenomenon.
Download full-text PDF |
Source |
---|
Alzheimers Dement
December 2024
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; NYU Langone Health, New York, NY, USA.
Background: Clinical and preclinical evidence suggest that abnormal electrical activity strongly impacts outcomes in Alzheimer's disease (AD). Indeed, AD patients with interictal spikes (IIS) show faster cognitive decline than those without IIS. Furthermore, seizures in patients with AD have been suggested to accelerate disease progression.
View Article and Find Full Text PDFBackground: Early changes in network activity serve as distinctive hallmarks in tauopathies such as Alzheimer's Disease and Frontotemporal Dementia. Decades before the onset of cognitive decline, many patients experience seizures which exacerbate the condition. Despite the recognised etiological overlaps between tauopathies and epilepsies, the relationship between tau and the development of circuit hyperexcitability is unclear and needs further investigation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Background: Cytoplasmic inclusions of TDP-43 are the primary pathology in the majority of ALS and FTLD cases. Recent reports in cell and animal models suggest TDP-43 pathology may enhance neuronal excitability, which could contribute to neurodegeneration via excitotoxicity. Dox-regulatable rNLS8 mice express human TDP-43 with mutations in the nuclear localization signal (hTDP-43NLSm) to promote cytoplasmic accumulation.
View Article and Find Full Text PDFBackground: Seizures in Alzheimer's Disease (AD) are increasingly recognized to occur and can increase cognitive decline and reduce survival compared to unaffected age-matched peers (Lyou et al. 2018). Administration of antiseizure medicines (ASMs) to AD patients with epileptiform activity may improve cognition (Vossel et al.
View Article and Find Full Text PDFBackground: Early-onset Alzheimer's disease (EOAD) associated with amyloid precursor protein (APP) duplications or presenilin (PSEN) variants increases risk of seizures. Targeting epileptiform activity with antiseizure medicine (ASM) administration to AD patients may beneficially attenuate cognitive decline (Vossel et al, JAMA Neurology 2021). However, whether mechanistically distinct ASMs differentially suppress seizures in discrete EOAD models is understudied (Lehmann et al, Neurochem Res 2021).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!