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Accepted manuscript

Association of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and Neurogenesis: A Systematic Review

Published online by Cambridge University Press:  14 February 2025

Hezekiah C.T. Au Open the ORCID record for Hezekiah C.T. Au [Opens in a new window] ,
Yang Jing Zheng Open the ORCID record for Yang Jing Zheng [Opens in a new window] ,
Gia Han Le ,
Sabrina Wong ,
Kayla M. Teopiz ,
Angela T.H. Kwan ,
Hartej Gill ,
Sebastian Badulescu ,
Kyle Valentino  and
Joshua D. Rosenblat
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Hezekiah C.T. Au
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada
Yang Jing Zheng
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada
Gia Han Le
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Sabrina Wong
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
Kayla M. Teopiz
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada
Angela T.H. Kwan
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Hartej Gill
Affiliation:
Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Sebastian Badulescu
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Kyle Valentino
Affiliation:
Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
Joshua D. Rosenblat
Affiliation:
Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
Rodrigo B. Mansur
Affiliation:
Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Canada
Roger S. McIntyre*
Affiliation:
Department of Psychiatry, University of Toronto, Toronto, Canada
*
*Corresponding Author: Dr. Roger S. McIntyre, Brain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada
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Abstract

Objective

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroproliferative effects and modulatory effects in neuronal pathways. Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on neurogenesis.

Methods

We examined studies that investigate changes in neurogenesis mediated by GLP-1 and GLP-1 RA administration in both human and animal populations. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to July 2nd. Primary studies investigating the role of GLP-1 and GLP-1 RAs on neurogenesis were included for analysis.

Results

GLP-1 and GLP-1 RAs (i.e. exenatide, geniposide, liraglutide, lixisenatide, and semaglutide), increased neurogenesis within the dentate gyrus, hippocampus, olfactory bulb, and the medial striatum in animal models. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in multiple apoptotic pathways and upregulating survival pathways.

Discussion

GLP-1 and GLP-1 RAs are positively associated with neurogenesis. This effect may have translational implications insofar as disparate mental disorders that are characterized by neurogenesis defects (e.g. depressive disorders and neurocognitive disorders) may be benefitted by these agents.

Keywords

Glucagon-Like PeptideGLP-1 Receptor AgonistNeurogenesisObesitySemaglutideLiraglutideExentaideTirzepatideLixisenatide
Type
Review Article
Information
Acta Neuropsychiatrica , Accepted manuscript , pp. 1 - 25
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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