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

Abstract

A burgeoning literature documents the confluence of ovarian steroids and central serotonergic systems in the injuction 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 activation of 5-HT3 and 5-HT1A receptors tending to impede focal and generalized seizures, while depletion of brain 5-HT along with 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 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 well be exploited for combinatorial drug therapy against epileptogenesis.

Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study

“…Serotonin may be implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors has not been fully established. Animal studies have shown that both an increase and decrease of brain serotonin may decrease the threshold for seizures [13,14,22]. Females had higher serotonin levels.…”

“…Low serotonin levels do not cross the BBB, but high levels are shown to cause BBB breakdown [13]. While low levels of serotonin decrease the threshold for seizures [14], high levels, such as during an overdose of selective serotonin reuptake inhibitors, are known to cause 'serotonin syndrome', which is characterized by seizures and muscle wasting, features also observed in OAE [15,16].…”

Neurosteroids and Seizure Activity

“…Studies are available in which the authors point to antiepileptic, and even neuroprotective, effects of estrogen. The hormone decreases neuronal death during seizures through up-regulation of the prosurvival molecule-Bcl-2, anti-oxidant potential as well as protection of NPY interneurons (82). In addition, it was demonstrated that the examined steroids caused "the induction of dendritic spine proliferation on serotonin neurons thus thawing a profound effect on serotonergic transmission" by the activation of 5-HT3 and 5-HT1A receptors (82).…”

“…The case is more difficult to prove with estrogen, because this hormone displays both pro- ( 79 – 81 ) and anticonvulsant properties ( 82 ), its mechanisms of actions being not fully understood. It is suspected that estrogen works through intracellular estrogen receptors, ER-alpha and ER-beta, which are found in nuclei of some neurons, e.g.…”

QbD approached comparison of reaction mechanism in microwave synthesized gold nanoparticles and their superior catalytic role against hazardous nirto‐dye

“…Recently, gold nanoparticles are emerging as unique, efficient, simple and reliable solutions for scientific and technical challenges of existing processes, machines or systems in various disciplines of engineering sciences . Discovery of new drugs or pharmaceutical combinations for the treatment of many life threating complex clinical conditions such as opportunistic infections, delayed wound healing, MDR (Multidrug resistance) bacterial and cancerous diseases, as well as epilepsy; not only required suitability and rationality in approaches and their selection but also proven to be time consuming exercise at the cost of exploiting limited and valuable resources in bulk . Most of the conventional nanoparticles and catalytic reactions facing limited success in term of efficiency of reaction yield as well as requires strict controlling of desired conditions .…”