Granulocyte-colony stimulating factor ameliorates irradiation-induced suppression of hippocampal neurogenesis in adult mice

Granulocyte-colony stimulating factor (G-csf) is a member of the hematopoietic growth factor family and demonstrates neuroprotective functions in neurodegenerative diseases. This study evaluated the radioprotective effects of G-csf in the suppression of hippocampal neurogenesis in adult mice undergoing irradiation. The radioprotective effects were assessed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical markers of neurogenesis, including the proliferating cell marker Ki-67 and the immature progenitor neuron marker doublecortin (DCX). Acute exposure to cranial irradiation (5 Gy γ-rays) induced neural apoptosis and inhibited neurogenesis in the dentate gyrus (DG) of the adult mouse hippocampus. Pretreatment with G-csf (100 μg/kg every 12 h subcutaneously on three consecutive days) attenuated neural apoptosis and decreased the number of Ki-67- and DCX-positive cells in the DG of the irradiated mouse hippocampus. Therefore, G-csf inhibited the detrimental effects of irradiation on hippocampal neurogenesis, suggesting that G-csf administration has potential therapeutic utility in brain irradiation.

Research highlights▶ Granulocyte-colony stimulating factor (G-csf) demonstrates neuroprotective functions in neurodegenerative diseases. ▶ Cranial irradiation induces neural apoptosis and inhibits neurogenesis in the dentate gyrus of the adult mouse hippocampus. ▶ Pretreatment with G-csf attenuated neural apoptosis and decreased rate of neurogenesis in the DG of the irradiated mouse hippocampus. ▶ The neuroprotective effects of G-csf observed in this study are consistent with similar observations in other brain injury models ▶ G-csf inhibits the detrimental effects of irradiation on hippocampal neurogenesis, suggesting that G-csf administration has potential therapeutic utility in brain irradiation.