【摘要】 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。更多还原

【Abstract】 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 137 Cs γ rays at an absorbed dose of 4.0 Gy. Mice in the IR+EE group were housed in EE for 35 d 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 ± 5.80 vs. 2.99 ± 6.18, p<0.05), had fewer DCX positive cells(123.8 ± 9.3 vs. 70.2 ± 5.9, p<0.05), and had a remarkably lower level of p-CREB/CREB(1.007 ± 0.058 vs. 0.772 ± 0.039, p<0.05). Compared with the IR group, the IR+EE group had an enhanced discrimination ratio(2.99 ± 6.18 vs. 28.31 ± 7.30, p<0.05), more DCX positive cells(70.2 ± 5.9 vs. 95.7 ± 6.5, p<0.05), and up-regulated the expression of p-CREB/CREB(0.772 ± 0.039 vs. 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.更多还原