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Updated: Feb 17, 2026
Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Golgi fragmentation induced by overactivated cyclin-dependent kinase 5 is associated with isoflurane-induced
Fang-Fang Miao1, Cui-Cui Kong1, Yan Wu2
1Department of Anesthesiology, Xuanwu Hospital.
Abstract:
Overactivated cyclin-dependent kinase 5 (Cdk5) induces Golgi fragmentation, which interrupts the processing and trafficking of secretory cargo and subsequently synaptic plasticity and synaptogenesis, and even leads to neuronal cell death. Cdk5 overactivation and subsequent Golgi fragmentation are involved in many neurodegenerative diseases. However, whether isoflurane-induced neurotoxicity is relevant to aberrant Cdk5 activation and subsequent Golgi fragmentation remains unknown. In the present study, we explored the underlying molecular mechanisms of isoflurane-induced neurotoxicity in primary cultured hippocampal neurons. After treatment with 2% isoflurane for 6 h, immunofluorescence staining and transmission electron microscopy were used to examine the Golgi structure. Neuronal viability was evaluated using the 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and TUNEL staining. Cdk5 activity was assessed using histone H1 as a substrate. Our results showed that Cdk5 activity and the number of fragmented Golgi increased significantly after isoflurane exposure. This was accompanied by an increase in neuronal death. Meanwhile, pharmacological inhibition of Cdk5 activity by 8 µM roscovitine alleviated isoflurane-induced Golgi fragmentation and neurotoxicity. Cumulatively, this study shows that aberrant Cdk5 activation-induced Golgi fragmentation is relevant to isoflurane neurotoxicity and indicates that a Cdk5 inhibitor may be a potential therapeutic candidate for the prevention of isoflurane-induced neurotoxicity. Video abstract: http://links.lww.com/WNR/A445.
Insights
Isoflurane exposure increases cyclin-dependent kinase 5 (Cdk5) activity, causing Golgi fragmentation and neuronal death. Inhibiting Cdk5 protects against isoflurane-induced neurotoxicity, suggesting Cdk5 inhibitors as potential therapeutics.
Area of Science:
- Neuroscience
- Molecular Biology
- Anesthesiology
Background:
- Overactivated cyclin-dependent kinase 5 (Cdk5) leads to Golgi fragmentation, impairing neuronal function and survival.
- Cdk5 overactivation and Golgi fragmentation are implicated in neurodegenerative diseases.
- The role of Cdk5 and Golgi fragmentation in isoflurane-induced neurotoxicity is not well understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying isoflurane-induced neurotoxicity in primary cultured hippocampal neurons.
- To determine if aberrant Cdk5 activation and subsequent Golgi fragmentation are involved in isoflurane neurotoxicity.
Main Methods:
- Primary cultured hippocampal neurons were exposed to 2% isoflurane for 6 hours.
- Golgi structure was examined using immunofluorescence staining and transmission electron microscopy.
- Neuronal viability was assessed via MTT assay and TUNEL staining; Cdk5 activity was measured using histone H1 substrate.
Main Results:
- Isoflurane exposure significantly increased Cdk5 activity and Golgi fragmentation.
- Neuronal death was elevated following isoflurane treatment.
- Pharmacological inhibition of Cdk5 with roscovitine attenuated isoflurane-induced Golgi fragmentation and neurotoxicity.
Conclusions:
- Aberrant Cdk5 activation and subsequent Golgi fragmentation are implicated in isoflurane-induced neurotoxicity.
- Cdk5 inhibitors show potential as therapeutic agents to prevent isoflurane neurotoxicity.
