Serotonin abnormalities in Dravet syndrome mice before and after the age of seizure onset.

Abstract:

:Dravet syndrome (DS) is a genetic form of severe epilepsy often associated with mutation of the SCN1A gene encoding the voltage gated sodium channel Nav1.1. Typically refractive to conventional therapy, serotonin neurotransmission may be an innovative target for treatment. To further understand the role of serotonin in this disorder, in this study we examined the state of the endogenous serotonin system in an Scn1a+/- mouse model of DS. Examined at an age before seizures appear, we found the hypothermic effect of 5-HT1A receptor agonist administration was attenuated. HPLC analysis of brain monoamine content revealed modestly reduced serotonin levels in tissue samples of the midbrain that included the dorsal raphe nucleus but no changes elsewhere in the brain. The reduced sensitivity to 5-HT1A agonist administration seen at young ages reversed after the age of seizure development when mice showed an exaggerated hypothermic response. Likewise, adult DS mice showed a pronounced hypersensitivity to a 5-HT2A/2C agonist. As adults however monoamine levels were not detectably altered. Thus there are alterations in the endogenous serotonin system that both precede and follow the appearance of seizure in DS mice, most strikingly in the response to agonist administration.

journal_name

Brain Res

journal_title

Brain research

authors

Hatini PG,Commons KG

doi

10.1016/j.brainres.2019.146399

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

146399

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(19)30453-6

journal_volume

1724

pub_type

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