中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (3): 491-500.doi: 10.4103/1673-5374.245473

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

父亲运动训练可调节雄性大鼠后代海马全局DNA甲基化的状态

  

  • 出版日期:2019-03-15 发布日期:2019-03-15

Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring

Christiano Spindler1, 2, Ethiane Segabinazi1, 2, André Luís Ferreira de Meireles1, 2, Francele Valente Piazza1, 2, Filipe Mega1, 2, Gabriela dos Santos Salvalaggio2, Matilde Achaval1, 2, Viviane Rostirola Elsner3, Simone Marcuzzo1, 2   

  1. 1 Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
    2 Laboratório de Histofisiologia Comparada, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
    3 Programa de Pós-Graduação em Biociências e Reabilitação, Centro Universitário Metodista-IPA, Porto Alegre, RS, Brazil
  • Online:2019-03-15 Published:2019-03-15
  • Contact: Simone Marcuzzo, PhD, simone.marcuzzo@ufrgs.br.

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摘要：

母亲运动训练有益于后代认知水平已得到公识，但父亲运动的影响尚未得到探讨。为评估父亲运动训练对雄性后代海马记忆和学习、神经可塑性和DNA甲基化水平的影响，实验将成年雄性Wistar大鼠随机分成2组：久坐父亲的后代或运动父亲的后代。父亲的孕前运动项目包括跑步机运动， 20min/d，每周连续5d，持续22d，而母亲没有接受训练。交配后，收集父亲精子进行全局DNA甲基化分析。在雄性后代出生后第53天（P53），以ELISA法和免疫组化法检测海马BrdU的细胞存活率，并确定突触素，reelin，脑源性神经营养因子（BDNF）和全局DNA甲基化水平的表达。并于生后47-51d以Morris水迷宫测试评估后代的空间记忆和学习变化。结果发现相较于久坐父亲的后代，运动父亲的后代空间学习能力明显改善，海马全局DNA甲基化水平明显下降；然而，在神经可塑性生物标志物BDNF，reelin和BrdU，以及父亲精子全局DNA甲基化的水平方面，久坐和运动父亲后代中未见到明显差异。这些结果表明父亲运动训练有益于雄性后代认知水平的提高，这可能与雄性后代的海马表观遗传编程有关。

orcid: 0000-0001-5705-5879(Simone Marcuzzo)

关键词: 表观遗传学, 孕前, 甲基化, 学习, 跑步机, 表观遗传编程, 遗传, 精子, 大鼠, 神经再生

Abstract:

It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2’-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2′-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear.

Key words: epigenetics, preconception, methylation, learning, treadmill running, fetal programming, inheritance, sperm, nerve regeneration