ArticleBrain and behavior2021
Inhibition of RhoA/Rho kinase signaling pathway by fasudil protects against kainic acid-induced neurite injury.
Article in Brain and behavior, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Targeting ROCK2 to Restore Epileptic Synaptic Networks via Mitophagy Activation: Insights from Translational Imaging of SV2A In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Insights into Calpain Activation and Rho-ROCK Signaling in Parkinson's Disease and Aging.Biomedicines · 2024Review
- Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies.Neural regeneration research · 2024Article
- Pharmacological inhibition of S6K1 rescues synaptic deficits and attenuates seizures and depression in chronic epileptic rats.CNS neuroscience & therapeutics · 2024Article
- The functional and molecular roles of p75 neurotrophin receptor (p75Journal of central nervous system disease · 2024Review
- Flavonoids fromZhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Mitochondria targeting drugs for neurodegenerative diseases-Design, mechanism and application.Acta pharmaceutica Sinica. B · 2022Review
- The role of Rho/ROCK in epileptic seizure-related neuronal damage.Metabolic brain disease · 2022Review
- Inhibition of RhoA/Rho kinase signaling pathway by fasudil protects against kainic acid-induced neurite injury.Brain and behavior · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimRhoA/Rho kinase pathway is essential for regulating cytoskeletal structure. Although its effect on normal neurite outgrowth has been demonstrated, the role of this pathway in seizure-induced neurite injury has not been revealed. The research examined the phosphorylation level of RhoA/Rho kinase signaling pathway and to clarify the effect of fasudil on RhoA/Rho kinase signaling pathway and neurite outgrowth in kainic acid (KA)-treated Neuro-2A cells and hippocampal neurons.
methodWestern blotting analysis was used to investigate the expression of key proteins of RhoA/Rho kinase signaling pathway and the depolymerization of actin. After incubated without serum to induce neurite outgrowth, Neuro-2A cells were fixed, and immunofluorescent assay of rhodamine-phalloidin was applied to detect the cellular morphology and neurite length. The influence of KA on neurons was detected in primary hippocampal neurons. Whole-cell patch clamp was conducted in cultured neurons or hippocampal slices to record action potentials.
resultKA at the dose of 100-200 μmol/L induced the increase in phosphorylation of Rho-associated coiled-coil-containing protein kinase and decrease in phosphorylation of Lin11, Isl-1 and Mec-3 kinase and cofilin. The effect of 200 μmol/L KA was peaked at 1-2 hours, and then gradually returned to baseline after 8 hours. Pretreatment with Rho kinase inhibitor fasudil reversed KA-induced activation of RhoA/Rho kinase pathway and increase in phosphorylation of slingshot and 14-3-3, which consequently reduced the ratio of G/F-actin. KA treatment induced inhibition of neurite outgrowth and decrease in spines both in Neuro-2a cells and in cultured hippocampal neurons, and pretreatment with fasudil alleviated KA-induced neurite outgrowth inhibition and spine loss.
conclusionThese data indicate that inhibiting RhoA/Rho kinase pathway might be a potential treatment for seizure-induced injury.
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