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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis

Author(s): Faheem Hyder Pottoo*, Md. Noushad Javed, Md. Abul Barkat, Md. Sabir Alam, Javaid Ashraf Nowshehri, Dhafer Mahdi Alshayban and Mohammad Azam Ansari*

Volume 17, Issue 3, 2019

Page: [214 - 231] Pages: 18

DOI: 10.2174/1570159X16666180628164432

Price: $65

Abstract

A burgeoning literature documents the confluence of ovarian steroids and central serotonergic systems in the injunction of epileptic seizures and epileptogenesis. Estrogen administration in animals reduces neuronal death from seizures by up-regulation of the prosurvival molecule i.e. Bcl-2, anti-oxidant potential and protection of NPY interneurons. Serotonin modulates epileptiform activity in either direction i.e administration of 5-HT agonists or reuptake inhibitors leads to the activation of 5-HT3 and 5-HT1A receptors tending to impede focal and generalized seizures, while depletion of brain 5-HT along with the destruction of serotonergic terminals leads to expanded neuronal excitability hence abatement of seizure threshold in experimental animal models. Serotonergic neurotransmission is influenced by the organizational activity of steroid hormones in the growing brain and the actuation effects of steroids which come in adulthood. It is further established that ovarian steroids bring induction of dendritic spine proliferation on serotonin neurons thus thawing a profound effect on serotonergic transmission. This review features 5-HT1A and 5-HT3 receptors as potential targets for ameliorating seizure-induced neurodegeneration and recurrent hypersynchronous neuronal activity. Indeed 5-HT3 receptors mediate cross-talk between estrogenic and serotonergic pathways, and could be well exploited for combinatorial drug therapy against epileptogenesis.

Keywords: Epileptic seizures, epileptogenesis, neuroprotection, estrogen, serotonin, neuronal plasticity.

Graphical Abstract

[1]
Goldenberg MM. Overview of drugs used for epilepsy and seizures: Etiology, diagnosis, and treatment. P&T 2010; 35(7): 392-415.
[PMID: 20689626]
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