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

Nickesha C. Anderson; Meghan A. Van Zandt; Swechhya Shrestha; Daniel B. Lawrence; Jyoti Gupta; Christopher Y. Chen; Felicia A. Harrsch; Trinithas Boyi; Carolyn E. Dundes; Gloster Aaron; Janice R. Naegele; Laura Grabel

Stem Cell Research (Dec 2018)

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

Nickesha C. Anderson,
Meghan A. Van Zandt,
Swechhya Shrestha,
Daniel B. Lawrence,
Jyoti Gupta,
Christopher Y. Chen,
Felicia A. Harrsch,
Trinithas Boyi,
Carolyn E. Dundes,
Gloster Aaron,
Janice R. Naegele,
Laura Grabel

Affiliations

Nickesha C. Anderson: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA; Corresponding author at: Shanklin Hall Atwater Labs, Biology Department, 52 Lawn Ave, Middletown, CT 06459, USA.
Meghan A. Van Zandt: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA
Swechhya Shrestha: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA
Daniel B. Lawrence: 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
Jyoti Gupta: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA
Christopher Y. Chen: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA
Felicia A. Harrsch: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA
Trinithas Boyi: 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
Carolyn E. Dundes: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA
Gloster Aaron: 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
Janice R. Naegele: 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
Laura Grabel: Dept. of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT 06459, USA

Journal volume & issue: Vol. 33
pp. 83 – 94

Abstract

Read online

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. Keywords: GABAergic interneuron progenitors, Embryonic stem cells, Electrophysiological analyses, Hippocampal-dependent spatial memory, Temporal lobe epilepsy

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

About the journal