Zhang Xing-Mei, Zhu Shun-Wei, Duan Rui-Sheng, Mohammed Abdul H, Winblad Bengt, Zhu Jie
Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
Neurotoxicology. 2008 May;29(3):406-12. doi: 10.1016/j.neuro.2008.01.006. Epub 2008 Feb 8.
Some epidemiological studies concerning gender differences in Alzheimer's disease (AD) support the higher prevalence and incidence of AD in women, while most studies using animal models of aging have included only male subjects. It is still uncommon for aged males and females to be compared in the same study. In the present study, we investigated how age and gender influence the excitotoxic neurodegeneration by treating C57BL/6 mice (aged females and males as well as adult females and males) with kainic acid (KA) intranasally. Clinical signs, behavioural changes, pathological changes and astrocyte proliferation were tested; and the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were measured after KA treatment. The results showed that aged female mice were more sensitive to KA-induced excitotoxicity as demonstrated by severer seizure activity, increased locomotion and rearing in open-field test, prominent hippocampal neuronal damage, enhanced astrocyte proliferation compared with aged males, adult females and adult male mice. In addition, higher BDNF level in hippocampus of aged female mice was observed. These results denote the disparity of aging and gender in KA-induced hippocampal neurodegeneration and aged female mice are more sensitive to the excitotoxicity.
一些关于阿尔茨海默病（AD）性别差异的流行病学研究支持女性中AD的患病率和发病率较高，而大多数使用衰老动物模型的研究仅纳入了雄性受试者。在同一研究中对老年雄性和雌性进行比较的情况仍然不常见。在本研究中，我们通过对C57BL/6小鼠（老年雌性和雄性以及成年雌性和雄性）鼻内注射海藻酸（KA），研究年龄和性别如何影响兴奋性毒性神经退行性变。测试了临床症状、行为变化、病理变化和星形胶质细胞增殖；并在KA处理后测量了脑源性神经营养因子（BDNF）和神经生长因子（NGF）的水平。结果表明，与老年雄性、成年雌性和成年雄性小鼠相比，老年雌性小鼠对KA诱导的兴奋性毒性更敏感，表现为癫痫活动更严重、旷场试验中的运动和竖毛增加、海马神经元损伤突出、星形胶质细胞增殖增强。此外，观察到老年雌性小鼠海马中BDNF水平较高。这些结果表明在KA诱导的海马神经退行性变中衰老和性别的差异，老年雌性小鼠对兴奋性毒性更敏感。
