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

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

Volume: 17 Issue: 3

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

Affiliation:

• Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University (Formerly University of Dammam), Dammam 31441,Saudi Arabia

• Department of Epidemic Disease Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441,Saudi Arabia

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

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.

Cite this article as:

Pottoo Hyder Faheem *, Javed Noushad Md., Barkat Abul Md. , Alam Sabir Md. , Nowshehri Ashraf Javaid, Alshayban Mahdi Dhafer and Ansari Azam Mohammad *, Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis, Current Neuropharmacology 2019; 17 (3) . https://dx.doi.org/10.2174/1570159X16666180628164432