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

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. © 2013 tzeng et al.; licensee biomed central ltd.