Effects of advanced maternal age on cognitive and emotional development in offspring rats.

Due to socio-economic development, an increasing number of women delay childbirth to their late 30 s and older. However, this delay brings a series of health problems to pregnant women and their offspring. The few studies on the effects of advanced maternal age (AMA) on offspring development, especially regarding neurocognitive and emotional development, reported mixed results. We examined the relationship between AMA and the performance of immature offspring of 3- versus 12-month-old Sprague-Dawley rat females on neurocognitive development tests and the possible mechanism of this relationship; the rats were individually housed with a randomly selected 3-month-old male, and the cognitive development of the offspring was evaluated by behavior tests including the Morris water maze, elevated plus maze, forced swimming and 3-chambered social behavior tests. Moreover, hematoxylin-eosin (HE) staining and Nissl staining were conducted to detect differences in the hippocampal morphology of the offspring, and Western blot analysis was conducted to detect the protein expression of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB) and phosphorylated CREB (pCREB). The behavior tests detected defects in the AMA rats compared with the control group. The HE and Nissl staining results showed no significant difference. However, the expression of BDNF, CREB and pCREB was reduced in the immature offspring of AMA rats compared with that in control rats. Based on our results, CREB-dependent expression of BDNF may be responsible for the damage to cognitive and emotional development in offspring caused by delayed motherhood.