Human stem cell-derived gabaergic interneurons establish efferent synapses onto host neurons in rat epileptic hippocampus and inhibit spontaneous recurrent seizures

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F21%3A10435044" target="_blank" >RIV/00216208:11130/21:10435044 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jlaIaZeP0M" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=jlaIaZeP0M</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms222413243" target="_blank" >10.3390/ijms222413243</a>

Result language

angličtina

Original language name

Human stem cell-derived gabaergic interneurons establish efferent synapses onto host neurons in rat epileptic hippocampus and inhibit spontaneous recurrent seizures

Original language description

Epilepsy is a complex disorder affecting the central nervous system and is characterised by spontaneously recurring seizures (SRSs). Epileptic patients undergo symptomatic pharmacolog-ical treatments, however, in 30% of cases, they are ineffective, mostly in patients with temporal lobe epilepsy. Therefore, there is a need for developing novel treatment strategies. Transplantation of cells releasing γ-aminobutyric acid (GABA) could be used to counteract the imbalance between ex-citation and inhibition within epileptic neuronal networks. We generated GABAergic interneuron precursors from human embryonic stem cells (hESCs) and grafted them in the hippocampi of rats developing chronic SRSs after kainic acid-induced status epilepticus. Using whole-cell patch-clamp recordings, we characterised the maturation of the grafted cells into functional GABAergic inter-neurons in the host brain, and we confirmed the presence of functional inhibitory synaptic connections from grafted cells onto the host neurons. Moreover, optogenetic stimulation of grafted hESC-derived interneurons reduced the rate of epileptiform discharges in vitro. We also observed decreased SRS frequency and total time spent in SRSs in these animals in vivo as compared to non-grafted controls. These data represent a proof-of-concept that hESC-derived GABAergic neurons can exert a therapeutic effect on epileptic animals presumably through establishing inhibitory synapses with host neurons.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

<a href="/en/project/NU21-08-00533" target="_blank" >NU21-08-00533: Targeted gene therapy for pharmacoresistant focal epilepsy</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Molecular Sciences

ISSN

1661-6596

e-ISSN

—

Volume of the periodical

22

Issue of the periodical within the volume

24

Country of publishing house

CH - SWITZERLAND

Number of pages

24

Pages from-to

13243

UT code for WoS article

000738111800001

EID of the result in the Scopus database

2-s2.0-85120695922