高龄妊娠对子代大鼠前额叶皮层神经干细胞增殖及突触可塑性的影响

Effects of advanced maternal age on the proliferation and synaptic plasticity of neural stem cells in the prefrontal cortex of offspring rats

目的探究高龄妊娠对子代大鼠前额叶皮层神经干细胞增殖及突触可塑性的影响。方法选择3月龄与12月龄SD雌性大鼠,均与3月龄SD雄性大鼠合笼。子代鼠出生后,将其分为适龄子代组(Con组)和高龄子代组(AMA组)。取出生后1 d的子代大鼠脑组织,利用HE染色观察前额叶皮层神经元的形态变化;利用qRT-PCR和Western blot方法分别检测前额叶皮层中G蛋白信号调节蛋白2(RGS2)、巢蛋白(Nestin)、突触后致密区蛋白95(PSD95)、脑源性神经营养因子(BDNF)和突触素(SYN)的mRNA及其蛋白质表达变化情况。结果HE染色结果发现,与Con组比较,AMA组前额叶皮层的神经元数目减少,部分神经元发生变性,出现胞体肿胀、空泡化现象。qRT-PCR和Western blot结果发现,与Con组比较,AMA组Nestin、RGS2、PSD95、BDNF、SYN mRNA及蛋白质相对表达水平均显著下降(P<0.05)。结论高龄孕鼠子代前额叶皮层的神经干细胞增殖能力减弱,突触可塑性能力降低,可能是造成子代脑发育障碍和认知功能下降的原因之一。

Objective:To investigate the impact of advanced maternal age on neural stem cell proliferation and synaptic plasticity in the prefrontal cortex of offspring rats.Methods:Female SD rats aged 3 months and 12 months were mated with male SD rats aged 3 months.The resulting offspring were divided into two groups:control group and advanced maternal age(AMA)group.Prefrontal cortical brain tissue was collected from newborns one day after birth,and HE staining was conducted to observe morphological changes in neurons of prefrontal cortex.qRT-PCR and Western blot techniques were utilized to measure mRNA and protein expression levels of G protein signaling regulator 2(RGS2),Nestin,postsynaptic density protein 95(PSD95),brain-derived neurotrophic factor(BDNF),and synaptophysin(SYN)in the prefrontal cortex.Results:Compared to the control group,HE staining revealed a reduction in the number of neurons in the prefrontal cortex of the AMA group,accompanied by neuronal degeneration characterized by cellular body swelling and vacuolization.qRT-PCR and Western blot analysis demonstrated significantly lower mRNA and protein expression levels of Nestin,RGS2,PSD95,BDNF,and SYN in the AMA group compared to the control group(P<0.05).Conclusions:The proliferation and synaptic plasticity of neural stem cells in the prefrontal cortex are diminished in offspring from rats with advanced maternal age,potentially contributing to the developmental disorders of brain and cognitive decline.