Not all rat pups are treated equally: Behavioral, neural, and (epi)genetic mechanisms mediating mother-offspring dynamics

并非所有的幼鼠都受到平等对待:行为、神经和(表观)遗传机制介导母子动态

基本信息

  • 批准号:
    RGPIN-2015-05229
  • 负责人:
  • 金额:
    $ 4.15万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2019
  • 资助国家:
    加拿大
  • 起止时间:
    2019-01-01 至 2020-12-31
  • 项目状态:
    已结题

项目摘要

Mothering quality relies on the integrity of multiple physiological and behavioural systems, and on early experiences that impact how a mother mothers. This proposal focuses on the dynamics of mother-pup interactions at the behavioural, neurophysiological, and (epi)genetic levels. I hypothesize that the effects of maternal care on offspring behaviour and neurophysiology depend upon individual characteristics of both mother and offspring, and the interaction between mother and offspring. Our recent NSERC-funded studies have focused on sources of inter-individual differences in mothering. Our approach has been to explore the variety of behavioural systems and their neurophysiologies that are activated in the new mother that contribute to the quality, intensity, and timing of maternal behavior with offspring, including mother's impulsivity, attention, reward processing, and memory, which in turn are affected by mother's own early experiences. We have also examined hormone and neurotransmitter systems involved in the regulation of mother-pup dynamics, including corticosterone, striatal dopamine, dopamine and oxytocin receptors, brain plasticity, and genetics and gene expression dopamine and serotonin systems at transcript and protein levels in relevant brain areas. However, with the exception of our most recent study, all our previous work has focused on factors that affect the mother, and we have assumed that mother responds in a uniform fashion to different offspring. The next phase of our research extends this work by focusing on factors that regulate mothers' DIFFERENTIAL parenting towards different pups in the litter and the differences in early experiences acquired by these individual pups that leads to differences in their subsequent development. Here we also drill down on brain areas associated with mothering and the genetic and epigenetic mechanisms that account for effects of differential mothering on the development of their subsequent mothering and associated behaviors and underlying brain mechanisms; to this end we will explore both within- and between-litter interactions between mother and pups. We will use genetic analyses in dopamine systems in outbred rats combined with epigenetic analyses and studies of pup cues and maternal factors that regulate maternal attention and nurturing in the mother rat. At the neurophysiological level, we will examine relationships between dopamine single-nucleotide polymorphism genetic and DNA methylation epigenetic variations, dopamine neurotransmitter systems and mother-pup dynamics. This research program will provide an explanation of mechanisms that mediate variations in parenting and its effects on offspring (F1 generation) at multiple levels, and inform research in human development where differential and transgenerational parenting are emerging foci of interest.
育儿质量取决于多种生理和行为系统的完整性,以及影响母亲方式的早期经验。这一建议侧重于在行为、神经生理和(EPI)遗传水平上的母崽相互作用的动态。我假设,母亲护理对后代行为和神经生理学的影响取决于母亲和子女的个体特征,以及母亲和子女之间的相互作用。我们最近由NSERC资助的研究集中在育儿方面个体间差异的来源。我们的方法是探索在新母亲身上激活的各种行为系统及其神经生理学,这些系统有助于母亲与后代的行为的质量、强度和时机,包括母亲的冲动、注意力、奖励处理和记忆,这些反过来又受到母亲自身早期经历的影响。我们还研究了参与母子动态调节的激素和神经递质系统,包括皮质酮、纹状体多巴胺、多巴胺和催产素受体、大脑可塑性,以及相关脑区转录和蛋白质水平的遗传和基因表达的多巴胺和5-羟色胺系统。然而,除了我们最近的研究之外,我们之前的所有工作都集中在影响母亲的因素上,我们假设母亲对不同的后代做出统一的反应。我们下一阶段的研究将通过集中于调节母亲对不同幼崽的不同育儿方式的因素,以及这些个体幼崽获得的早期经验的差异,从而导致它们随后发展的差异来扩展这项工作。在这里,我们还将深入研究与育儿相关的大脑区域,以及解释不同育儿对其后续育儿发展的影响的遗传和表观遗传机制,以及相关的行为和潜在的大脑机制;为此,我们将探索母亲和幼崽之间的内部和幼崽之间的互动。我们将结合表观遗传学分析和对幼鼠线索和母体因素的研究,对杂交大鼠的多巴胺系统进行遗传分析,以调节母鼠的母体注意力和养育。在神经生理学水平上,我们将研究多巴胺单核苷酸多态遗传和DNA甲基化表观遗传变异、多巴胺神经递质系统和母崽动态之间的关系。这项研究计划将在多个层面上解释父母教养方式变化的调节机制及其对后代(F1代)的影响,并为人类发育研究提供信息,其中差异和跨代养育是新出现的感兴趣的焦点。

项目成果

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Fleming, Alison其他文献

Maternal Perceptions of Paternal Investment Are Associated With Relationship Satisfaction and Breastfeeding Duration in Humans
  • DOI:
    10.1037/fam0000468
  • 发表时间:
    2018-12-01
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Cost, Katherine Tombeau;Jonas, Wibke;Fleming, Alison
  • 通讯作者:
    Fleming, Alison
Conjugation to increase treatment volume during local therapy: a case study with PEGylated camptothecin
  • DOI:
    10.1021/bc700214h
  • 发表时间:
    2007-11-01
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
    Haverstick, Kraig;Fleming, Alison;Saltzman, W. Mark
  • 通讯作者:
    Saltzman, W. Mark

Fleming, Alison的其他文献

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{{ truncateString('Fleming, Alison', 18)}}的其他基金

Not all rat pups are treated equally: Behavioral, neural, and (epi)genetic mechanisms mediating mother-offspring dynamics
并非所有的幼鼠都受到平等对待:行为、神经和(表观)遗传机制介导母子动态
  • 批准号:
    RGPIN-2015-05229
  • 财政年份:
    2016
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Discovery Grants Program - Individual
Not all rat pups are treated equally: Behavioral, neural, and (epi)genetic mechanisms mediating mother-offspring dynamics
并非所有的幼鼠都受到平等对待:行为、神经和(表观)遗传机制介导母子动态
  • 批准号:
    RGPIN-2015-05229
  • 财政年份:
    2015
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Discovery Grants Program - Individual
Canadian Research Chair in Behavioural Neurobiology and Genetics
加拿大行为神经生物学和遗传学研究主席
  • 批准号:
    1000202844-2005
  • 财政年份:
    2012
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Canada Research Chairs
Maternal behaviour and prefrontal function in the rat
大鼠的母性行为和前额叶功能
  • 批准号:
    273-2008
  • 财政年份:
    2012
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Discovery Grants Program - Individual
Canadian Research Chair in Behavioural Neurobiology and Genetics
加拿大行为神经生物学和遗传学研究主席
  • 批准号:
    1000202844-2005
  • 财政年份:
    2011
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Canada Research Chairs
Maternal behaviour and prefrontal function in the rat
大鼠的母性行为和前额叶功能
  • 批准号:
    273-2008
  • 财政年份:
    2011
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Discovery Grants Program - Individual
Canadian Research Chair in Behavioural Neurobiology and Genetics
加拿大行为神经生物学和遗传学研究主席
  • 批准号:
    1000202844-2005
  • 财政年份:
    2010
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Canada Research Chairs
Maternal behaviour and prefrontal function in the rat
大鼠的母性行为和前额叶功能
  • 批准号:
    273-2008
  • 财政年份:
    2010
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Discovery Grants Program - Individual
Canadian Research Chair in Behavioural Neurobiology and Genetics
加拿大行为神经生物学和遗传学研究主席
  • 批准号:
    1000202844-2005
  • 财政年份:
    2009
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Canada Research Chairs
Maternal behaviour and prefrontal function in the rat
大鼠的母性行为和前额叶功能
  • 批准号:
    273-2008
  • 财政年份:
    2009
  • 资助金额:
    $ 4.15万
  • 项目类别:
    Discovery Grants Program - Individual

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妊娠期间膳食叶酸摄入量和小鼠幼崽雄性生殖细胞的表观遗传分析。
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Not all rat pups are treated equally: Behavioral, neural, and (epi)genetic mechanisms mediating mother-offspring dynamics
并非所有的幼鼠都受到平等对待:行为、神经和(表观)遗传机制介导母子动态
  • 批准号:
    RGPIN-2015-05229
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并非所有的幼鼠都受到平等对待:行为、神经和(表观)遗传机制介导母子动态
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