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Updated: Jul 12, 2025
Pentylenetetrazole-Induced Kindling Mouse Model
Published on: June 12, 2018
Decrease of Cellular Communication Network Factor 1 (CCN1) Attenuates PTZ-Kindled Epilepsy in Mice
Yiwei Liao1,2, Sha Huang2,3,4, Yuhu Zhang5
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Abstract:
To investigate the molecular mechanism of communication network factor 1 (CCN1) regulating pentylenetetrazol (PTZ)-induced epileptogenesis, deepen the understanding of epilepsy seizure pathogenesis, and provide new drug action targets for its clinical prevention and treatment. Differentially expressed genes (DEGs) on microarrays GSE47516 and GSE88992 were analyzed online using GEO2R. Pathway enrichment and protein-protein interaction network (PPI) analysis of DEGs were carried out using Metascape. Brain tissue samples of severe traumatic brain injury patients (named Healthy group) and refractory epilepsy patients (named Epilepsy group) were obtained and analyzed by qRT-PCR and immunohistochemistry (IHC) staining. A PTZ-induced epilepsy mouse model was established and verified. Morphological changes of neurons in mouse brain tissue were detected using hematoxylin and eosin (HE) staining. qRT-PCR was conducted to detect the mRNA expressions of apoptosis-associated proteins Bax, Caspase-3 and bcl2. TUNEL staining was performed to detect brain neuron apoptosis. The levels of myocardial enzymology, GSH, MDA and ROS in blood of mouse were detected by biochemical assay. CCN1 expression was increased in epilepsy brain tissue samples. CCN1 decreasing effectively prolongs seizure incubation period and decreases seizure duration. Silencing of CCN1 also reduces neuronal damage and apoptosis, decreases mRNA and protein expression of proapoptotic proteins Bax and Caspase-3, increases mRNA expression of antiapoptotic protein Bcl2. Moreover, decrease of CCN1 decreases myocardial enzymatic indexes CK and CK-MB levels, reduces myocardial tissue hemorrhage, and relieves oxidative stress response in hippocampal and myocardial tissue. CCN1 expression is increased in epileptic samples. CCN1 decreasing protects brain tissue by attenuating oxidative stress and inhibiting neuronal apoptosis triggered by PTZ injection, which probably by regulating Nrf2/HO-1 pathway.
Insights
Communication network factor 1 (CCN1) is elevated in epilepsy and contributes to seizure pathogenesis. Reducing CCN1 protects the brain by decreasing neuronal apoptosis and oxidative stress, offering potential therapeutic targets for epilepsy.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Epileptogenesis involves complex molecular mechanisms.
- Communication network factor 1 (CCN1) role in epilepsy is not fully understood.
- Identifying novel therapeutic targets for epilepsy is crucial.
Purpose of the Study:
- To elucidate the molecular mechanism of CCN1 in pentylenetetrazol (PTZ)-induced epileptogenesis.
- To deepen the understanding of epilepsy seizure pathogenesis.
- To identify potential drug targets for clinical prevention and treatment of epilepsy.
Main Methods:
- Analysis of differentially expressed genes (DEGs) from microarray datasets (GSE47516, GSE88992) using GEO2R.
- Pathway enrichment and protein-protein interaction (PPI) network analysis via Metascape.
- qRT-PCR and immunohistochemistry (IHC) on human epilepsy and control brain tissues.
- Establishment and verification of a PTZ-induced epilepsy mouse model.
- Hematoxylin and eosin (HE) staining for neuronal morphology.
- qRT-PCR for apoptosis-related genes (Bax, Caspase-3, Bcl2).
- TUNEL staining for neuronal apoptosis.
- Biochemical assays for myocardial enzymes, GSH, MDA, and ROS.
Main Results:
- CCN1 expression was significantly increased in epilepsy brain tissues.
- Decreasing CCN1 prolonged seizure incubation and reduced seizure duration in a PTZ-induced epilepsy model.
- CCN1 silencing reduced neuronal damage and apoptosis, decreasing pro-apoptotic proteins (Bax, Caspase-3) and increasing anti-apoptotic protein (Bcl2).
- Reduced CCN1 levels decreased myocardial injury markers (CK, CK-MB), myocardial hemorrhage, and alleviated oxidative stress in hippocampal and myocardial tissues.
- CCN1 reduction protected brain tissue by attenuating oxidative stress and inhibiting neuronal apoptosis, likely via the Nrf2/HO-1 pathway.
Conclusions:
- CCN1 is upregulated in epilepsy and plays a critical role in PTZ-induced epileptogenesis.
- Downregulation of CCN1 demonstrates neuroprotective effects by inhibiting apoptosis and oxidative stress.
- CCN1 represents a promising therapeutic target for epilepsy treatment.
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