Allopregnanolone augments epileptiform activity of an in-vitro mouse hippocampal preparation in the first postnatal week.

Abstract:

:In the immature brain the neurotransmitter γ-amino butyric acid (GABA) mediates a membrane depolarization and can contribute to both, inhibition and excitation. Therefore the consequences of a positive modulation of GABA(A) receptors by neurosteroids on epileptiform activity are hard to predict. In order to analyze whether neurosteroids attenuate or exaggerate epileptiform activity in the immature brain, we investigated the effect of the neurosteroid allopregnanolone on epileptiform activity in an in-toto hippocampus preparation of early postnatal mice (postnatal days 4-7) using field potential recordings. These in-vitro experiments revealed that 0.5 μmol/L allopregnanolone had no effect on ictal-like epileptiform activity, but increased the occurrence of interictal epileptiform events. The allopregnanolone-induced enhancement of interictal epileptiform activity could be blocked by a selective inhibition of synaptic GABAA receptors. In contrast, allopregnanolone had no effect on interictal epileptiform activity upon enhanced extrasynaptic GABAergic activity. Patch-clamp experiments demonstrated that allopregnanolone prolonged the decay of GABAergic postsynaptic currents, but had no effect on tonic GABAergic currents. We conclude from these results that allopregnanolone can enhance excitability in the immature hippocampus viaprolonged synaptic GABAergic currents. This potential effect of neurosteroids on brain excitability should be considered if they are applied as anticonvulsants to premature or early postnatal babies.

journal_name

Epilepsy Res

journal_title

Epilepsy research

authors

Sharopov S,Winkler P,Uehara R,Lombardi A,Halbhuber L,Okabe A,Luhmann HJ,Kilb W

doi

10.1016/j.eplepsyres.2019.106196

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

106196

eissn

0920-1211

issn

1872-6844

pii

S0920-1211(19)30291-8

journal_volume

157

pub_type

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