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

这项研究计划旨在了解对早期父母照顾的干扰如何唤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更有意识和反应，例如吸入空气中二氧化碳浓度增加，以及痛苦刺激。我们将小鼠暴露在重复交叉养育(RCF)的范例中，给哺乳的雌性小鼠，而不是它们的亲生母亲。众所周知，RCF通过基因-环境相互作用增强呼吸反应，缓冲由过量二氧化碳引起的血液酸化。我们最近发现，一个编码pH敏感通道(酸敏离子通道1：ASIC1)的基因(Asic1)通过RCF过程变得表观遗传增强。相同的基因和相关的通道调节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，我们将评估呼吸对二氧化碳的超敏反应和改变的伤害性感觉是否在相同的个体中相关，以及它们是否在连续几代小鼠中共分离。通过最先进的技术，我们将测量RCF和正常饲养的动物在RCF之后大脑中的pH变化。 我们的研究将促进对早期生命发育的轻度到中度干预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反应的知识。它将提供一个可靠的、生态敏感的改变pH/ASIC活性的动物模型，使对早期逆境和表观遗传适应的呼吸和伤害性反应的药理学评估成为可能。这将加强加拿大在有机体对中度不利环境的适应性反应科学方面的声誉。

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.