Short- and long-term physiological adaptations to moderate interference with maternal care

对产妇护理的适度干扰的短期和长期生理适应

• 批准号: RGPIN-2016-06145
• 负责人: Battaglia, Marco
• 金额: $ 2.04万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=616124
• 关键词: Short; long; term; physiological; adaptations

This research plan is aimed at understanding how interferences with early-life parental cares evoke adaptive and potentially defensive physiological responses that render offspring more aware and reactive to some basic adversative stimuli, such as an augmented CO2 concentration in inhaled air, and painful stimuli. We expose mice to a paradigm of repeated cross fostering (RCF) to lactating females other than their biological mothers. The RCF is known to enhance the respiratory responses that buffer against blood acidification induced by excess of CO2 via gene-environment interaction. We recently found that a gene (asic1) that codify for a pH-sensing channel (acid-sensing ion channel 1: ASIC1) becomes epigenetically enhanced by the RCF procedure. The same gene and the related channel mediate sensitivity to painful stimuli, and we recently found that RCF mice are hypersensitive to painful stimuli. In this research we shall assess whether respiratory hypersensitivity to CO2 and altered nociception correlate within the same individuals, and if they co-segregate in successive generations of mice. By state of the art technology we shall measure how pH changes in the brain of RCF and normally-reared animals vary, following RCF. Our research will advance knowledge on how mild-to-moderate interference with early-life development affect multiple physiological traits and enhance respiratory and nociceptive adaptive responses to adversities. It will provide a reliable, ecologically sensible animal model of altered pH/ASIC activity, enabling pharmacological evaluations of respiratory and nociceptive responses to early adversities and epigenetic adaptation. This will strengthen Canada’s reputation in science applied to organismic adaptive response to moderately adverse environments.

该研究计划旨在了解对生命早期父母照顾的干扰如何引起适应性和潜在的防御性生理反应，使后代对一些基本的不利刺激（例如吸入空气中二氧化碳浓度增加和疼痛刺激）更加敏感和反应。我们将小鼠置于与生母以外的哺乳期雌性重复交叉寄养（RCF）的范例中。已知 RCF 可以增强呼吸反应，通过基因-环境相互作用来缓冲过量 CO2 引起的血液酸化。我们最近发现编码 pH 感应通道（酸感应离子通道 1：ASIC1）的基因 (asic1) 通过 RCF 程序得到表观遗传增强。相同的基因和相关通道介导对疼痛刺激的敏感性，我们最近发现 RCF 小鼠对疼痛刺激高度敏感。在这项研究中，我们将评估同一个体内对二氧化碳的呼吸过敏和伤害感受改变是否相关，以及它们是否在连续几代小鼠中共同分离。通过最先进的技术，我们将测量 RCF 和正常饲养的动物大脑中 pH 值在 RCF 之后如何变化。 我们的研究将增进对早期生命发育的轻度至中度干扰如何影响多种生理特征并增强对逆境的呼吸和伤害性适应性反应的了解。它将提供一个可靠的、生态上敏感的改变 pH/ASIC 活性的动物模型，从而能够对早期逆境和表观遗传适应的呼吸和伤害性反应进行药理学评估。这将加强加拿大在应用于对适度不利环境的有机适应性反应的科学领域的声誉。