Excitatory amino acid transporter 1 supports adult hippocampal neural stem cell self-renewal

Joshua D. Rieskamp; Ileanexis Rosado-Burgos; Jacob E. Christofi; Eliza Ansar; Dalia Einstein; Ashley E. Walters; Valentina Valentini; John P. Bruno; Elizabeth D. Kirby

iScience (Jul 2023)

Excitatory amino acid transporter 1 supports adult hippocampal neural stem cell self-renewal

Joshua D. Rieskamp,
Ileanexis Rosado-Burgos,
Jacob E. Christofi,
Eliza Ansar,
Dalia Einstein,
Ashley E. Walters,
Valentina Valentini,
John P. Bruno,
Elizabeth D. Kirby

Affiliations

Joshua D. Rieskamp: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA
Ileanexis Rosado-Burgos: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA
Jacob E. Christofi: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA
Eliza Ansar: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA
Dalia Einstein: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA
Ashley E. Walters: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA
Valentina Valentini: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA; Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy
John P. Bruno: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA
Elizabeth D. Kirby: Department of Psychology, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA; Chronic Brain Injury Program, The Ohio State University, Columbus, OH 43210, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 7
p. 107068

Abstract

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Summary: Within the adult mammalian dentate gyrus (DG) of the hippocampus, glutamate stimulates neural stem cell (NSC) self-renewing proliferation, providing a link between adult neurogenesis and local circuit activity. Here, we show that glutamate-induced self-renewal of adult DG NSCs requires glutamate transport via excitatory amino acid transporter 1 (EAAT1) to stimulate lipogenesis. Loss of EAAT1 prevented glutamate-induced self-renewing proliferation of NSCs in vitro and in vivo, with little role evident for canonical glutamate receptors. Transcriptomics and further pathway manipulation revealed that glutamate simulation of NSCs relied on EAAT1 transport-stimulated lipogenesis. Our findings demonstrate a critical, direct role for EAAT1 in stimulating NSCs to support neurogenesis in adulthood, thereby providing insights into a non-canonical mechanism by which NSCs sense and respond to their niche.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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