Promotion of cAMP responsive element-binding protein activity ameliorates radiation-induced suppression of hippocampal neurogenesis in adult mice.

This study was performed to examine whether elevated activity of cAMP responsive element-binding protein (CREB) attenuates the detrimental effects of acute gamma (γ) -irradiation on hippocampal neurogenesis and related functions. C57BL/6 male mice were treated with rolipram (1.25 mg/kg, i.p., twice a day for 5 consecutive days) to activate the cAMP/CREB pathway against cranial irradiation (2 Gy) , and were euthanized at 24 h post-irradiation. Exposure to γ-rays decreased both CREB phosphorylation and immunohistochemical markers for neurogenesis, including Ki-67 and doublecortin (DCX) , in the hippocampal dentate gyrus (DG) . However, the rolipram treatment protected from γ-irradiation-induced decreases of CREB phosphorylation, and Ki-67 and DCX immunoreactivity in the hippocampal DG. In an object recognition memory test, mice trained 24 h after acute γ-irradiation (2 Gy) showed significant memory impairment, which was attenuated by rolipram treatment. The results suggest that activation of CREB signaling ameliorates the detrimental effects of acute γ-irradiation on hippocampal neurogenesis and related functions in adult mice.