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母体应激引起的青少年和成年后代变化:神经行为改善与端粒维持。

Maternal stress-induced changes in adolescent and adult offspring: Neurobehavioural improvement and telomere maintenance.

作者信息

Sivasangari Karunanithi, Sivamaruthi Bhagavathi Sundaram, Chaiyasut Chaiyavat, Rajan Koilmani Emmanuvel

机构信息

Behavioural Neuroscience Laboratory, Department of Animal Science, Bharathidasan University, Tiruchirappalli, India.

Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.

出版信息

Heliyon. 2023 Sep 21;9(10):e20385. doi: 10.1016/j.heliyon.2023.e20385. eCollection 2023 Oct.

Abstract

Maternal stress (MS) during gestation is known to increase the risk for the development of behavioural and physiological disorders and advances cellular aging. In this study, we investigated whether the supplementation of standardized extract (CDRI-08/BME) or l-Carnosine (L-C) to the mother exposed to social stress during gestation modify the effect on their offspring's neurobehaviour, antioxidant defence gene expression, telomere length, and telomere biology. To test this, timed pregnant rats were subjected to social stress during the gestational day (GD) 16-18. A subset of stressed pregnant rats received either BME [80 mg/kg in 0.5% gum acacia (per-orally; p.o)] or L-C [1 mg/kg (p.o)] every day from GD-10 to until their pup's attained postnatal day (PND)-23. We observed that MS induced anxiety-like behaviour, altered inter-limb coordination, antioxidant defence genes [Superoxide dismutase (SOD1,2), Catalase (CAT), Glutathione peroxidase-3 (GPX3)], telomerase reverse transcriptase (TERT), shelterin complex subunits (TRF1, RAP1B, POT1) protein level and shorten telomere length. Notably, supplementation of BME/L-C dampens the MS, thus the effect on neurobehaviour, antioxidant defence gene expression, and telomere biology is minimized in their offspring. Together, our results suggest that supplementation of BME/L-C during gestation dampens the MS and reduced oxidative stress-mediated changes in telomere shortening/biology and associated neurobehaviour in offspring born following MS.

摘要

已知孕期母体应激(MS)会增加行为和生理紊乱的发生风险,并加速细胞衰老。在本研究中,我们调查了在孕期遭受社会应激的母体补充标准化提取物(CDRI - 08/BME)或L - 肌肽(L - C)是否会改变对其后代神经行为、抗氧化防御基因表达、端粒长度和端粒生物学的影响。为了验证这一点,对定时受孕的大鼠在妊娠第16 - 18天施加社会应激。一部分应激受孕大鼠从妊娠第10天开始每天接受BME [80 mg/kg溶于0.5%阿拉伯树胶(经口;p.o)] 或L - C [1 mg/kg(经口)],直至其幼崽达到出生后第23天(PND - 23)。我们观察到,MS诱导了焦虑样行为,改变了肢体间协调性、抗氧化防御基因[超氧化物歧化酶(SOD1,2)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶 - 3(GPX3)]、端粒酶逆转录酶(TERT)、端粒保护蛋白复合体亚基(TRF1、RAP1B、POT1)的蛋白水平,并缩短了端粒长度。值得注意的是,补充BME/L - C可减轻MS,因此对其后代的神经行为、抗氧化防御基因表达和端粒生物学的影响最小化。总之,我们的结果表明,孕期补充BME/L - C可减轻MS,并减少MS后出生的后代中氧化应激介导的端粒缩短/生物学变化及相关神经行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2ea/10520813/b7afe3d6f82b/ga1.jpg

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