Nimodipine Promotes Neurite Outgrowth and Protects Against Neurotoxicity in PC12 Cells

Overview

Journal Iran J Basic Med Sci

Publisher Mashhad University of Medical Sciences

Specialty General Medicine

Date 2021 Mar 1

PMID 33643570

Citations 3

Authors

Miduki Kusakabe

Yasushi Hasegawa

Affiliations

Soon will be listed here.

Abstract

Objectives: Nimodipine is an L-type voltage-dependent calcium channel (VDCC) antagonist. However, the actions of nimodipine except calcium blocking are poorly understood. This study aimed to investigate the effect of nimodipine on neurite outgrowth and neuroprotection .

Materials And Methods: After PC12 cells were treated with different concentrations of nimodipine, neurite outgrowth was estimated using the ImageJ software. Neuroprotective effects of nimodipine against HO and calcium ionophore-induced neurotoxicity were investigated using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the activation of extracellular signal-regulated kinase (ERK) and cyclic AMP-response element-binding protein (CREB) pathway was investigated for clarifying the action mechanism of nimodipine.

Results: Nimodipine treatment at doses of higher than 10 µM induced neurite outgrowth in the cells. Additionally, VDCC knockdown by siRNA significantly suppressed the nimodipine-induced neurite outgrowth in PC12 cells, suggesting that the drug promotes neurite outgrowth by binding to VDCC. HO and calcium ionophore induce oxidative and calcium stress in PC12 cells. Nimodipine exhibited neuroprotective effects against HO- and calcium ionophore-induced neurotoxicity by increasing the mRNA expression levels of neurotrophic factors, calcium-binding proteins, and antioxidants that are transcribed by CREB activation.

Conclusion: This is the first report that nimodipine induces neurite outgrowth and exerts its neuroprotective activity through the ERK/CREB signaling pathway in PC12 cells.

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