Association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and neurogenesis: a systematic review

Feb 14, 2025Acta neuropsychiatrica

Link between glucagon-like peptide-1 receptor agonists and brain cell growth: a systematic review

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Abstract

GLP-1 and GLP-1 receptor agonists may increase neurogenesis in several brain regions.

GLP-1 and GLP-1 receptor agonists have been observed to increase neurogenesis in the dentate gyrus, hippocampus, olfactory bulb, and medial striatum in animal models.
Modulatory effects were noted in multiple apoptotic pathways related to neurogenesis.
GLP-1 and GLP-1 receptor agonists are associated with the upregulation of survival pathways in neuronal systems.
These findings suggest potential benefits for mental disorders characterized by neurogenesis defects.

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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 characterised by neurogenesis defects (e.g. depressive disorders and neurocognitive disorders) may be benefitted by these agents.

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Association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and neurogenesis: a systematic review

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