BACKGROUNDS: Cranial gamma-ray irradiation is one of the effective treatments for brain tumors. So far, we have found that nasal administration of oxytocin prevents cognitive dysfunction in gamma-irradiated mice, and restores reduction in mRNA expression of KCC2, a chloride ion transporter (Igarashi et al., BBRC, 2022). However, it remains unclear how oxytocin is involved in the increased expression of KCC2.
METHODS: 3-week-old male C57BL6/J mice were exposed to a 60Co source for 4 minutes and irradiated with 1.5 Gy gamma rays. Irradiation was performed once a day and repeated for 3 days. Mice in the oxytocin-administered group were nasally administered 0.1 mM oxytocin 5 μL after each irradiation. Hippocampal tissue was excised from gamma-irradiated mice, mice treated with oxytocin after gamma-irradiation, and non-gamma-ray irradiated mice, and the amounts of phosphorylated CREB and phosphorylated ERK1/2 were examined by Western blot.
RESULTS: In mouse hippocampus administered nasally with oxytocin after gamma-irradiation, phosphorylated CREB was reduced by approximately 24% compared with non-gamma-irradiated mice (p <0.05). In addition, mice nasally administered oxytocin after gamma irradiation had a 51% decrease in phosphorylated CREB (p<0.001) compared to non-irradiated mice, and a 35% decrease compared to gamma-irradiated mice (p<0.05). In the mouse hippocampus to which oxytocin was nasally administered after gamma-irradiation, the phosphorylated ERK1/2 was increased by about 24% as compared with the non-gamma-ray-irradiated mouse, but it was not significant.
DISCUSSION: In this study, we found that phosphorylated CREB decreased in mice treated with oxytocin after gamma irradiation. Previous studies have suggested that phosphorylated CREB is involved in the reduction of KCC2 expression (Rivera et al., J. Neurosci. 2004). From these facts, it is considered that oxytocin administration after gamma-ray irradiation may lead to an increase in the expression level of KCC2 through a decrease in phosphorylated CREB.