title: Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid.
abstract: 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.
  
  
  RESULTS
  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.
authors: Tsai-Teng
authors: TT
authors: Tzeng
authors: Huey-Jen
authors: HJ
authors: Tsay
authors: Luping
authors: L
authors: Chang
authors: Chia-Lin
authors: CL
authors: Hsu
authors: Tzu-Hsuan
authors: TH
authors: Lai
authors: Fong-Lee
authors: FL
authors: Huang
authors: Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei 112, Taiwan. yshiao@nricm.edu.tw.
authors: Young-Ji
authors: YJ
authors: Shiao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D057967:Infusions, Intraventricular; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects
chemical_list: C505409:Casp3 protein, mouse; D053148:Caspase 3; D007608:Kainic Acid