丰富环境改善小鼠放射性认知功能障碍

Environmental enrichment improves irradiation-induced cognitive dysfunction

探讨丰富环境(Environmental Enrichment, EE)对电离辐射所致小鼠认知功能障碍的保护作用及其可能机制。将36只雌性昆明小鼠随机分为对照组(Control)、辐射组(IR)和辐射丰富环境组(IR+EE)。IR组和IR+EE组小鼠采用137Csγ射线进行全身辐照至吸收剂量4 Gy;IR+EE组小鼠辐照后给予连续35 d EE刺激。采用新物体识别实验检测小鼠认知功能;免疫组织化学方法检测海马区神经发生标记物双皮质素(Doublecortin, DCX)及磷酸化环磷酸腺苷应答元件结合蛋白(Phosphorylatedcyclicadenosinemonophosphate(cAMP)response element-binding protein, p-CREB)的表达;Western blot方法检测海马区CREB及p-CREB蛋白的表达。结果表明:与对照组相比,IR组小鼠新物体分辨率明显降低(45.55±5.80 vs. 2.99±6.18,p<0.05),海马区DCX阳性细胞数明显减少(123.8±9.3 vs. 70.2±5.9,p<0.05),p-CREB/CREB表达下调(1.007±0.058 vs. 0.772±0.039,p<0.05);而予以EE刺激后小鼠新物体分辨率明显回升(2.99±6.18 vs. 28.31±7.30,p<0.05),海马区DCX阳性细胞数明显增加(70.2±5.9 vs. 95.7±6.5,p<0.05),p-CREB/CREB表达上调(0.772±0.039 vs. 1.014±0.093,p<0.05)。结果提示EE可能是通过上调海马区p-CREB的表达,保护海马神经发生,进而改善辐射所致的小鼠认知功能障碍。

To investigate the protective effect and potential mechanism of environmental enrichment (EE)on irradiation-induced cognitive dysfunction in mice,thirty-six female Kunming mice were randomly divided into three groups administered different treatments:control,Irradiation (IR),and IR+EE.The mice in IR group and IR+EE group were irradiated with 137Csγ rays at an absorbed dose of 4.0Gy.Mice in the IR+EE group were housed in EE for 35d following irradiation.The object recognition task was used to evaluate the cognitive function of mice.The expression of the neurogenesis marker doublecortin (DCX),and phosphorylated cAMP response element-binding protein (p-CREB)was detected by using immunohistochemical staining.The expression of the cAMP response element-binding protein (CREB)and p-CREB proteins in hippocampus was assayed by using western blotting.The results showed that compared with control group,the irradiation group had a low discrimination ratio in the object recognition task (45.55±5.80vs.2.99±6.18,p<0.05),had fewer DCX positive cells (123.8±9.3vs.70.2±5.9, p<0.05),and had a remarkably lower level of p-CREB/CREB (1.007±0.058vs.0.772±0.039,p<0.05).Compared with the IR group,the IR+EE group had an enhanced discrimination ratio (2.99±6.18vs.28.31±7.30,p<0.05), more DCX positive cells (70.2±5.9vs.95.7±6.5,p<0.05),and up-regulated the expression of p-CREB/CREB (0.772±0.039vs.1.014±0.093,p<0.05).The results suggest that EE may alleviate irradiation-induced cognitive dysfunction and impair neurogenesis via enhancing hippocampal p-CREB expression.