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The effect of simvastatin on picrotoxin-induced seizure in mice
Murat Kesim1, Esin Yulug, Mine Kadioglu
1Faculty of Medicine, Department of Pharmacology, Karadeniz Technical University, Trabzon, Turkey. muratkesim@gmail.com
Objective:
To study the effect of simvastatin on picrotoxin-induce seizures in mice in order to understand the impact of gabaergic system on neuronal cell death.
Methods:
The study was held between July and September 2011, at the Karadeniz Technical University in Trabzon, Turkey. Balb/c mice weighting 20-40g were randomly selected and divided into five groups of six each. The first group was designated as control group; and the second as the picrotoxin (10mg/kg; intraperitoneal) alone group. The rest of the groups were administered simvastatin in dozes of 10, 20 and 40mg/kg respectively. Onset, number and duration of seizures, and death time were measured in mice for one hour. At the end of the study, the brain was removed from mice and normal and degenerative pyramidal neurons were counted in hippocampal CA1, CA2, CA3 region by light microscope. Using SPSS 17, Mann=Whitney U and Chi square and student-T tests were performed for statistical analysis.
Results:
Simvastatin (10mg/kg) significantly decreased the number and duration of picrotoxin-induced seizures in mice. In addition, Simvastatin (10, 20, and 40mg/kg) significantly reduced the total number of abnormal pyramidal cells in CA1 and CA3 hippocampal regions compared to the picrotoxin-alone group.
Conclusion:
The effect of simvastatin on picrotoxin-induced seizures may be the result of increase in gabaergic activity and decrease in glutamatergic activity. More studies are needed to validate these results.
Insights
Simvastatin reduced seizures and neuronal damage in mice, suggesting a role in modulating the gabaergic system. Further research is needed to confirm these findings on neuronal cell death.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Picrotoxin-induced seizures provide a model to study the gabaergic system's role in neuronal function.
- Neuronal cell death is a critical factor in seizure-related brain damage.
Purpose of the Study:
- To investigate the neuroprotective effects of simvastatin against picrotoxin-induced seizures in mice.
- To explore the impact of simvastatin on neuronal cell death in the hippocampus.
Main Methods:
- Balb/c mice were divided into control, picrotoxin-alone, and simvastatin-treated groups (10, 20, 40 mg/kg).
- Seizure parameters (onset, number, duration) and survival time were recorded.
- Histopathological analysis of hippocampal neurons (CA1, CA2, CA3) was performed.
Main Results:
- Simvastatin (10 mg/kg) significantly reduced the number and duration of picrotoxin-induced seizures.
- All tested doses of simvastatin significantly decreased the count of abnormal pyramidal neurons in the CA1 and CA3 hippocampal regions.
Conclusions:
- Simvastatin demonstrates anticonvulsant and neuroprotective effects in a mouse model of seizures.
- These effects may be mediated by modulation of the gabaergic and glutamatergic systems.
- Further studies are warranted to elucidate the precise mechanisms involved.
