Institute of Molecular Genetics, RAS, 2 Akademika Kurchatova square, Moscow 123182, Russia.
Lomonosov Moscow State University, Biological Faculty, 1-12 Leninskie gori, Moscow 119234, Russia.
Neuropeptides. 2021 Apr;86:102114. doi: 10.1016/j.npep.2020.102114. Epub 2020 Dec 28.
Selective serotonin reuptake inhibitors (SSRI) are commonly used to treat depression during pregnancy. SSRIs cross the placenta and may influence the maturation of the foetal brain. Clinical and preclinical findings suggest long-term consequences of SSRI perinatal exposure for the offspring. The mechanisms of SSRI effects on developing brain remain largely unknown and there are no directional approaches for prevention of the consequences of maternal SSRI treatment during pregnancy. The heptapeptide Semax (MEHFPGP) is a synthetic analogue of ACTH(4-10) which exerts marked nootropic and neuroprotective activities. The aim of the present study was to investigate the long-term effects of neonatal exposure to the SSRI fluvoxamine (FA) in white rats. Additionally, the study examined the potential for Semax to prevent the negative consequences of neonatal FA exposure. Rat pups received FA or vehicle injections on postnatal days 1-14, a time period equivalent to 27-40 weeks of human foetal age. After FA treatment, rats were administered with Semax or vehicle on postnatal days 15-28. During the 2nd month of life, the rats underwent behavioural testing, and monoamine levels in brain structures were measured. It was shown that neonatal FA exposure leads to the impaired emotional response to stress and novelty and delayed acquisition of food-motivated maze task in adolescent and young adult rats. Furthermore, FA exposure induced alterations in the monoamine levels in brains of 1- and 2- month-old rats. Semax administration reduced the anxiety-like behaviour, improved learning abilities and normalized the levels of brain biogenic amines impaired by the FA exposure. The results demonstrate that early-life FA exposure in rat pups produces long-term disturbances in their anxiety-related behaviour, learning abilities, and brain monoamines content. Semax exerts a favourable effect on behaviour and biogenic amine system of rats exposed to the antidepressant. Thus, peptide Semax can prevent behavioural deficits caused by altered 5-HT levels during development.
选择性 5-羟色胺再摄取抑制剂（SSRIs）常用于治疗妊娠期抑郁症。SSRIs 可穿过胎盘，并可能影响胎儿大脑的成熟。临床和临床前研究表明，围产期暴露于 SSRIs 对后代有长期影响。SSRIs 对发育中大脑的影响机制在很大程度上尚不清楚，也没有针对预防妊娠期母亲 SSRIs 治疗后果的定向方法。七肽 Semax（MEHFPGP）是 ACTH（4-10）的合成类似物，具有显著的益智和神经保护作用。本研究的目的是研究新生期暴露于 SSRIs 氟伏沙明（FA）对白鼠的长期影响。此外，该研究还研究了 Semax 预防新生 FA 暴露的负面后果的潜力。新生大鼠在出生后第 1-14 天接受 FA 或载体注射，这相当于人类胎儿年龄的 27-40 周。FA 治疗后，大鼠在出生后第 15-28 天接受 Semax 或载体治疗。在生命的第 2 个月，大鼠进行行为测试，并测量大脑结构中的单胺水平。结果表明，新生 FA 暴露导致青春期和成年早期大鼠对压力和新奇事物的情绪反应受损，以及获得食物动机迷宫任务的能力延迟。此外，FA 暴露导致 1-2 月龄大鼠大脑中单胺水平发生改变。Semax 给药减少了焦虑样行为，改善了学习能力，并使 FA 暴露导致的大脑生物胺水平正常化。研究结果表明，新生期 FA 暴露会导致幼鼠的焦虑相关行为、学习能力和大脑单胺类物质含量长期紊乱。Semax 对暴露于抗抑郁药的大鼠的行为和生物胺系统产生有利影响。因此，肽 Semax 可以预防发育过程中 5-HT 水平改变引起的行为缺陷。
