Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, P.O. Box: 1465613111, Tehran, Iran.
Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Neurochem Res. 2018 May;43(5):1067-1074. doi: 10.1007/s11064-018-2519-6. Epub 2018 Apr 3.
Evidence indicates that experiencing early-life stress (ELS) is a risk factor for the development of mental disorders such as depression. Maternal separation stress (MS) is a valid animal model of ELS that caused to induce long-lasting effects on the brain and behaviors of animals. It hypothesized that adolescence is a critical stage in which the brain is still developing, and applying (non)pharmacological therapies in this period may attenuate the effects of ELS on the brain and behavior. Male rats were subjected to MS from postnatal day (PND) 2-14, and the stressed animals were then treated with (1) chronic fluoxetine (FLX) (5 mg/kg) and (2) voluntary running wheel exercise (RW) from PND 30, for 30 days. Then, we subjected the animals to behavioral and molecular assessments at PND 60. Our data showed that MS provoked depressive-like behaviors in rats, tested by the forced swimming test, splash test, and sucrose preference test. Additionally, we found that MS increased the gene expression of the NR2A (and not NR2B) subunit of N-methyl-D-aspartate (NMDA) receptors in the hippocampus of adult rats. Both FLX and RW treatments during adolescence were able to mitigate the negative effects of ELS on stressed animals. These results highlighted the importance of adolescence in treating stressed animals with FLX/voluntary RW exercise to alleviate the depressive effects of ELS. In addition, we found that ELS altered the transcriptional level of Grin2a (and not Grin2b) in the hippocampus. Finally, our results showed that FLX/voluntary RW exercise during adolescence could normalize altered expression of Grin2a in the hippocampus of adult rats.
有证据表明，经历早期生活压力（ELS）是精神障碍（如抑郁症）发展的一个风险因素。母体分离应激（MS）是 ELS 的一种有效动物模型，会对动物的大脑和行为产生持久影响。有假设认为青春期是大脑仍在发育的关键阶段，在此期间应用（非）药理学疗法可能会减轻 ELS 对大脑和行为的影响。雄性大鼠在出生后第 2-14 天接受 MS，然后在青春期（PND）30 天内用（1）慢性氟西汀（FLX）（5mg/kg）和（2）自愿跑步轮运动（RW）对压力动物进行治疗，持续 30 天。然后，我们在 PND 60 对动物进行行为和分子评估。我们的数据表明，MS 通过强迫游泳试验、飞溅试验和蔗糖偏好试验在大鼠中引发了类似抑郁的行为。此外，我们发现 MS 增加了成年大鼠海马体中 N-甲基-D-天冬氨酸（NMDA）受体的 NR2A（而不是 NR2B）亚基的基因表达。FLX 和 RW 在青春期的治疗都能够减轻 ELS 对压力动物的负面影响。这些结果强调了青春期在使用 FLX/自愿 RW 运动治疗应激动物以减轻 ELS 抑郁作用方面的重要性。此外，我们发现 ELS 改变了海马体中 Grin2a（而不是 Grin2b）的转录水平。最后，我们的结果表明，FLX/自愿 RW 运动在青春期可以使成年大鼠海马体中 Grin2a 的表达异常恢复正常。
