IMR Press / JIN / Volume 21 / Issue 5 / DOI: 10.31083/j.jin2105133
Open Access Original Research
Cdc42 Promotes Axonogenesis of Primary Hippocampal Neurons by Inhibiting Glycogen Synthase Kinase-3β
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1 Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, 510515 Guangzhou, Guangdong, China
2 NMPA Key Laboratory for Safety Evaluation of Cosmetics, 510515 Guangzhou, Guangdong, China
3 Experimental Education & Administration Center, School of Basic Medical Sciences, Southern Medical University, 510515 Guangzhou, Guangdong, China
*Correspondence: (Lin Zhang); (Hai-Hong Wang)
These authors contributed equally.
Academic Editor: Robert Friedman
J. Integr. Neurosci. 2022, 21(5), 133;
Submitted: 29 January 2022 | Revised: 28 March 2022 | Accepted: 30 March 2022 | Published: 22 July 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Progressive axon degeneration is a common pathological feature of neurodegenerative diseases. Cdc42 is a member of the Rho GTPase family that participates in axonogenesis. GSK-3β is a serine/threonine kinase highly implicated in neuronal development and neurodegeneration. This study aimed to examine whether cdc42 promotes axonogenesis by regulating GSK-3β activity. Methods: Hippocampal neurons were isolated from neonatal Sprague-Dawley rats and transfected with designated plasmid vectors to alter the activities of cdc42 and GSK-3β. LiCl treatment was used to inhibit the GSK-3β activity in primary neurons. GSK-3β activity was determined by an enzyme activity assay kit. Immunofluorescence staining was used to detect axons stained with anti-Tau-1 antibody and dendrites stained with anti-MAP2 antibody. Results: Transfection with an active cdc42 mutant (cdc42F28L) decreased the activity of GSK-3β and induced axonogenesis in primary rat hippocampal neurons, while transfection with a negative cdc42 mutant (cdc42N17) resulted an opposite effect. Moreover, transfection with plasmid vectors carrying wild-type GSK-3β or a constitutively active GSK3β mutant (GSK-3β S9A) increased the activity of GSK-3β and attenuated axonogenesis of primary hippocampal neurons with excessive cdc42 activity, whereas inhibition of GSK-3β by LiCl abolished the inhibitory effect of the negative cdc42 mutant on axonogenesis. Conclusions: This study suggests that cdc42 induces axonogenesis of primary rat hippocampal neurons via inhibiting GSK-3β activity. These findings support further investigation into the mechanisms of cdc42/GSK-3β-mediated axonogenesis.

hippocampal neurons
Fig. 1.
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