Pluripotent stem cell-derived interneuron progenitors mature and restore memory deficits but do not suppress seizures in the epileptic mouse brain.

Autor:	Anderson NC; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: ncanderson@wesleyan.edu., Van Zandt MA; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: mvanzandt@wesleyan.edu., Shrestha S; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: sshrestha@wesleyan.edu., Lawrence DB; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA; Program in Neuroscience and Behavior, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: dblawrence@wesleyan.edu., Gupta J; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: jgupta@wesleyan.edu., Chen CY; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: cychen@wesleyan.edu., Harrsch FA; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA., Boyi T; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA; Program in Neuroscience and Behavior, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: tboyi@wesleyan.edu., Dundes CE; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: cdundes@stanford.edu., Aaron G; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA; Program in Neuroscience and Behavior, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: gaaron@wesleyan.edu., Naegele JR; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA; Program in Neuroscience and Behavior, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: jnaegele@wesleyan.edu., Grabel L; Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA. Electronic address: lgrabel@wesleyan.edu.
Jazyk:	angličtina
Zdroj:	Stem cell research [Stem Cell Res] 2018 Dec; Vol. 33, pp. 83-94. Date of Electronic Publication: 2018 Oct 05.
DOI:	10.1016/j.scr.2018.10.007
Abstrakt:	GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived interneuron progenitors (hESNPs) could differentiate, correct hippocampal-dependent spatial memory deficits, and suppress seizures in a pilocarpine-induced TLE mouse model. We found that transplanted ventralized hESNPs differentiated into mature GABAergic interneurons and became electrophysiologically active with mature firing patterns. Some mice developed hESNP-derived tumor-like NSC clusters. Mice with transplants showed significant improvement in the Morris water maze test, but transplants did not suppress seizures. The limited effects of the human GABAergic interneuron progenitor grafts may be due to cell type heterogeneity within the transplants. (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu