J Korean Epilepsy Soc.  2006 Jun;10(1):3-10.

Minocycline Inhibits Caspase-Dependent Cell Death Pathway and is Neuroprotective against Hippocampal Damage after Kainic Acid-Induced Seizure in Mice

• Shin HY
• Cho YJ
• Cho KJ
• Kim HW
• Kim HJ
• Kim GW
• Lee BI
• Heo K

Abstract

PURPOSE: Despite current acceptance of its neuroprotective property, whether the minocycline affords neuroprotection or how it protects neurons against seizures in the animal model of epilepsy is not clear. This prompts us to investigate whether minocycline is neuroprotective against kainic acid (KA)-induced seizure in mice through inhibition of caspase-dependent mitochondrial apoptotic pathways.
METHODS
Adult male ICR mice were subjected to seizures by intrahippocampal KA injection with treatment of vehicle or minocycline. For cell death analysis, histological analysis using cresyl-violet staining, TdT-mediated dUTP-biotin nick end labeling (TUNEL), and histone-associated DNA fragmentation analysis were performed. Evaluation of cytochrome c, cleaved caspase-3, and caspase-3 activity were also performed.
RESULTS
Hippocampal neuronal death was evident by cresyl violet staining, TUNEL, and cell death assay in vehicle-treated mice after KA injection; however, there was significant reduction of cell death in the minocycline-treated group. Significant decrease of both cytosolic translocation of cytochrome c and subsequent activation of caspase-3 after treatment of minocycline were demonstrated by Western blot analysis, immunohistochemical staining, and caspase-3 activity assay.
CONCLUSION
This study suggests that minocycline may be neuroprotective against hippocampal damage after KA-induced seizure through inhibition of caspase-dependent cell death pathways.

Keyword

Minocycline; Seizure; Apoptosis; Caspase; Cytochrome c

MeSH Terms

Adult
Animals
Apoptosis
Blotting, Western
Caspase 3
Cell Death*
Cytochromes c
Cytosol
DNA Fragmentation
Epilepsy
Humans
In Situ Nick-End Labeling
Kainic Acid
Male
Mice*
Mice, Inbred ICR
Minocycline*
Models, Animal
Neurons
Seizures*
Viola
Caspase 3
Cytochromes c
Kainic Acid
Minocycline