Possible Involvement of Caspases in Proliferation of Neocortical Neural Stem/Progenitor Cells in the Developing Mouse Brain

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  • Yoneyama Masanori
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
  • Shiba Tatsuo
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
  • Yamaguchi Taro
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
  • Ogita Kiyokazu
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

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Abstract

Caspases are well-known enzymes that work as initiators and effectors of apoptosis. To elucidate the role of caspases in neurodevelopment, we sought to determine if caspases are involved in the proliferation of neural stem/progenitor cells (NPCs) in the developing mouse brain. Labeling with 5-bromo-2′-deoxyuridine (BrdU) from days 14 to 18 of pregnant mice revealed that the 18-d old fetus had many BudU-positive cells in its brain. Double-labeling revealed that active caspase-3 was co-localized with these BrdU-positive cells in the neocortex, hippocampus, and subventricular zone of the fetal brain. Active caspase-3 was detected in cultures of NPCs derived from the neocortex of 15-d old fetuses during culture periods. Importantly, the pan-caspase inhibitor z-VAD-FMK was effective at completely inhibiting neurosphere formation by the NPCs. These results suggest the possibility that the caspase cascade is essential for the proliferation of neocortical NPCs in the developing mouse brain.

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