This study was based on our previous report that the expression of active caspase-3 kept at a high level in dentate gyrus during postnatal development, which is not related to an apoptotic event. We addressed the hypothesis that the active caspase-3 expression may be related to a nonapoptotic role in the regulation of the cell cycle and differentiation or other physiological functions. To confirm this hypothesis, through a temporal investigation from postnatal day (P) 0, 4, 7, 10, 14, 21, 28, to 56, based on immunofluorescent method, we dual labeled active caspase-3 with Ki-67 or β-tubulin in the dentate gyrus. Our results showed a minority of active caspase-3 positive cells were colabeled with the proliferation marker Ki-67 in stratum moleculare (MOL), granular cell layer (GCL), subgranular zone (SGZ) and polymorphic stratum (POLY) from P0 to P14, and the colabeled cells decreased gradually with age. From P21 to P56, the colocalization of the two proteins was mainly focused on SGZ. There was a positive correlation between the positive cells of active caspase-3 with that of Ki-67. In addition, an extensive colocalization between active caspase-3 and β-tubulin was observed at all the age groups. There was a strong positive correlation between the intensity of active caspase-3 in GCL with that of β-tubulin in MOL, GCL and POLY of dentate gyrus and the stratum lucidum of CA3. Our data raised the possibility of a nonapoptotic role of active caspase-3 in dentate gyrus, which may be partly associated with cellular proliferation and differentiation, and also may be related to neurite outgrowth, axonal transport, or dendrite elongation of granular cells during postnatal development.

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