Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid

Journal of Biomedical Science

Young-Ji Shiao³  Fong-Lee Huang¹  Tzu-Hsuan Lai⁵  Chia-Lin Hsu⁴  Luping Chang⁴  Huey-Jen Tsay²  Tsai-Teng Tzeng⁵ 

[1] Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei 112, Taiwan;Institute of Neuroscience, Brain Research Center, school of life science, National Yang-Ming University, Taipei 112, Taiwan;National Research Institute of Chinese Medicine, NO. 155-1. Sec. 2, LiNung St., Peitou, Taipei, Taiwan;Division of Basic Chinease Medicine, National Research Institute of Chinese Medicine, Taipei 112, Taiwan;Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei 112, Taiwan

关键词: Hippocampus;    Neurogenesis;    Gliosis;    Caspase 3;    Neurodegeneration;    Kainic acid;    Epileptogenesis;   

Others  :  821689
DOI  :  10.1186/1423-0127-20-90

 received in 2013-08-13, accepted in 2013-12-02,  发布年份 2013

【 摘 要 】

Background

The roles of caspase 3 on the kainic acid-mediated neurodegeneration, dendritic plasticity alteration, neurogenesis, microglial activation and gliosis are not fully understood. Here, we investigate hippocampal changes using a mouse model that receive a single kainic acid-intracerebral ventricle injection. The effects of caspase 3 inhibition on these changes were detected during a period of 1 to 7 days post kainic acid injection.

Result

Neurodegeneration was assessed by Fluoro-Jade B staining and neuronal nuclei protein (NeuN) immunostaining. Neurogenesis, gliosis, neuritic plasticity alteration and caspase 3 activation were examined using immunohistochemistry. Dendritic plasticity, cleavvage-dependent activation of calcineurin A and glial fibrillary acidic protein cleavage were analyzed by immunoblotting. We found that kainic acid not only induced neurodegeneration but also arouse several caspase 3-mediated molecular and cellular changes including dendritic plasticity, neurogenesis, and gliosis. The acute caspase 3 activation occurred in pyramidal neurons as well as in hilar interneurons. The delayed caspase 3 activation occurred in astrocytes. The co-injection of caspase 3 inhibitor did not rescue kainic acid-mediated neurodegeneration but seriously and reversibly disturb the structural integrity of axon and dendrite. The kainic acid-induced events include microglia activation, the proliferation of radial glial cells, neurogenesis, and calcineurin A cleavage were significantly inhibited by the co-injection of caspase 3 inhibitor, suggesting the direct involvement of caspase 3 in these events. Alternatively, the kainic acid-mediated astrogliosis is not caspase 3-dependent, although caspase 3 cleavage of glial fibrillary acidic protein occurred.

Conclusions

Our results provide the first direct evidence of a causal role of caspase 3 activation in the cellular changes during kainic acid-mediated excitotoxicity. These findings may highlight novel pharmacological strategies to arrest disease progression and control seizures that are refractory to classical anticonvulsant treatment.

【 授权许可】

   
2013 Tzeng et al.; licensee BioMed Central Ltd.

【 图 表 】

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