Molecular mechanisms of sex differences in epilepsy and seizure susceptibility in chemical, genetic and acquired epileptogenesis


Reddy DS, Thompson W, Calderara G




Neurosci Lett . 2021 Apr 17;750:135753.

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This article provides a succinct overview of sex differences in epilepsy and putative molecular mechanisms underlying sex differences in seizure susceptibility in chemical, genetic, and acquired epileptogenesis.

The susceptibility to excitability episodes and occurrence of epileptic seizures are generally higher in men than women. The precise molecular mechanisms remain unclear, but differences in regional morphology and neural circuits in men and women may explain differential vulnerability to seizures and epileptogenic cascades.

Changes in seizure sensitivity can be attributed to steroid hormones, including fluctuations in neurosteroids as well as neuroplasticity in their receptor signaling systems. Other potential neurobiological bases for sex differences in epilepsies include differences in brain development, neurogenesis, neuronal chloride homeostasis, and neurotrophic and glial responses.

In catamenial epilepsy, a gender-specific neuroendocrine condition, epileptic seizures are most often clustered around a specific menstrual period in adult women.

A deeper understanding of the molecular and neural network basis of sex differences in seizures and response to antiepileptic drugs is highly warranted for designing effective, sex-specific therapies for epilepsy, epileptogenesis, and seizure disorders.

Copyright © 2021 Elsevier B.V. All rights reserved.

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