Sampino Silvestre, Stankiewicz Adrian Mateusz, Zacchini Federica, Goscik Joanna, Szostak Agnieszka, Swiergiel Artur Hugo, Drago Gaspare, Modlinski Jacek Andrzej, Ptak Grazyna Ewa
Department of Experimental Embryology, Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.
Faculty of Veterinary Medicine, University of Teramo, Italy.
J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1465-1473. doi: 10.1093/gerona/glx016.
There is growing evidence that advanced maternal age is a risk factor for neurological and neuropsychiatric disorders in offspring. However, it remains unclear whether the altered brain programming induced by advanced maternal age is mediated by pre- or postnatal factors. Here, a mouse model was used to investigate whether pregnancy at advanced age may provoke behavioral and brain gene expression changes in offspring. Swiss Albino mice conceived by 3-month-old males and either 15-18-month-old (n = 11) or 3-month-old control females (n = 5), were delivered by cesarean section, fostered after birth by 3-month-old dams and subjected to a battery of behavioral tests. Furthermore, genome-wide mRNA expression was analyzed in the hippocampi of 4-month-old males offspring using microarrays. Offspring conceived by old mothers exhibited increased ultrasound vocalization activity during separation from the foster mother, increased anxiety-like behaviors in adult life, and altered patterns of hippocampal gene expression, compared to controls. These effects were not reversed by the postnatal maternal care provided by the young foster mothers, suggesting that the altered brain programming is already established at birth, consistent with prenatal effects related to maternal aging.
越来越多的证据表明，高龄产妇是后代患神经和神经精神疾病的一个风险因素。然而，尚不清楚高龄产妇所导致的大脑程序改变是由产前还是产后因素介导的。在此，我们使用小鼠模型来研究高龄妊娠是否会引发后代的行为和大脑基因表达变化。由3个月大的雄性小鼠与15 - 18个月大的雌性小鼠（n = 11）或3个月大的对照雌性小鼠（n = 5）交配受孕的瑞士白化小鼠，通过剖宫产分娩，出生后由3个月大的母鼠抚养，并接受一系列行为测试。此外，使用微阵列分析了4个月大雄性后代海马体中的全基因组mRNA表达。与对照组相比，老年母亲所生的后代在与抚养母亲分离期间表现出超声发声活动增加、成年后焦虑样行为增加以及海马体基因表达模式改变。这些影响并没有被年轻抚养母亲提供的产后母性照料所逆转，这表明大脑程序的改变在出生时就已确立，这与与母亲年龄相关的产前影响一致。
