Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring
Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring
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高龄父母年龄受损的成年雌性大鼠后代的恐惧调节和海马有限公司
DOI：
10.1007/s11064-017-2306-9
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发表时间：
2017
影响因子：
4.4
通讯作者：
Jichuan Zhang
中科院分区：
文献类型：
--
作者：
Lilu Luo;Tingting Sun;Xin Guan;Yiling Ni;Liqiang Yang;Quan Zhao;Xiangyang Kong;Yanmei Chen;Jichuan Zhang
母亲或父亲的高龄与认知和情感障碍的风险增加有关。慢性压力也是人类生活中一种常见的导致精神疾病的经历。然而，这两个因素对后代的协同作用研究很少。在本研究中，幼鼠(3-4个月)和老年(12-14个月)大鼠的子代在4周龄时接受为期21天的CUMS。采用行为学和电生理学技术研究了高龄父母和慢性不可预测的轻度应激(CUMS)对儿童情绪和认知行为的影响及其相关的细胞机制。我们发现，无论是年长的还是年轻的育种者，CUMS都减少了蔗糖消耗，增加了焦虑，并损害了后代的学习和记忆。然而，父母年龄越大，对恐惧记忆和空间记忆的损害主要集中在雌性后代。雌性后代的血清皮质酮水平低于雄性，但随着亲代年龄的增加，雌性后代的血清皮质酮水平显著升高。此外，在年长父母的雌性后代中，海马体LTD严重受损。我们的结果表明，来自年龄较大的繁殖者的雌性后代可能对压力更敏感，海马体功能更脆弱。这些结果可能为今后防治高龄亲代相关精神障碍提供实验依据。
Advanced maternal or paternal age is associated with increased risks of cognitive and emotional disorders. Chronic stress is also a common experience in human life that causes psychiatric diseases. However, the synergistic effects of these two factors on offspring are rarely studied. In the present study, the offspring of both young (3–4 months) and old (12–14 months) rat parents were given CUMS for 21 days at the age of 4 weeks. The effects of advanced parental age and chronic unpredictable mild stress (CUMS) on emotional and cognitive behaviors and the related cellular mechanisms were investigated by using behavioral and electrophysiological techniques. We found that CUMS decreased sucrose consumption, increased anxiety, and impaired learning and memory in offspring from both old and young breeders. However, advanced parental age impaired fear memory and spatial memory mainly in female offspring. The serum corticosterone of female offspring was lower than males, but advanced parental age significantly elevated serum corticosterone in female offspring in response to electrical foot shocks. In addition, hippocampal LTD was severely impaired in female offspring from older parents. Our results indicated that female offspring from older breeders might be more sensitive to stress, and the hippocampal function was more vulnerable. These results might provide experimental basis for the prevention and treatment of advanced parental age related psychiatric disorders in future.