Motherhood, Oxytocin and the Medial Prefrontal Cortex

母性、催产素和内侧前额皮质

• 批准号: 8191697
• 负责人: BENEDETTA J LEUNER
• 金额: $ 24.34万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-02 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8191697
• 关键词: Address; Adult; Age; Anxiety; Architecture; Attention; Attenuated; Award; Behavior; Behavioral; Behavioral Assay; Brain; Brain region; Caring; Cognition; Cognitive; Data; Dendritic Spines; Endocrine; Environment; Estrogens; Evaluation; Excitatory Synapse; Exhibits; Female; Foundations; Glucocorticoids; Goals; Hormonal; Hormonal Change; Hormones; Human; Impaired cognition; Institution; Instruction; Journals; Learning; Letters; Link; Measures; Medial; Mediating; Memory; Mental Depression; Mental disorders; Mood Disorders; Mothers; Neuropeptides; Neurosciences; Ohio; Outcome; Oxytocin; Oxytocin Receptor; Parenting behavior; Phase; Play; Postpartum Period; Predisposition; Prefrontal Cortex; Process; Publishing; Rattus; Regulation; Research; Research Personnel; Research Project Grants; Research Proposals; Rewards; Rodent; Role; Site; Staging; Stress; Structure; Synaptic plasticity; Testing; Time; TimeLine; Universities; Update; Vertebrates; Woman; Work; adverse outcome; behavior measurement; brain behavior; cognitive function; density; design; experience; flexibility; hippocampal pyramidal neuron; improved; insight; male; motherhood; neuronal growth; offspring; programs; relating to nervous system; research study; resilience; stress management; way finding

The postpartum period is accompanied by dramatic clianges in hormones, including increased glucocorticoid and decreased estrogen levels. In virgin rodents, high glucocorticoid and low estrogen levels have been associated with diminished dendritic architecture and fewer dendritic spines, sites of excitatory synapses, in the medial prefrontal cortex (mPFC). This hormonal environment has also been shown to negatively impact behaviors mediated by the mPFC, by impairing cognitive function and enhancing anxiety. Despite the known detrimental effects of high glucocorticoid and low estrogen levels, mothers with this hormonal profile exhibit attenuated anxiety. In addition, research conducted during the K99 phase has shown that dendritic spine density is increased in the mPFC of mother rats and that this effect coincides with improved attention and behavioral flexibility, functions that depend on the mPFC. However, the factors that shield the maternal mPFC from the potentially damaging postpartum hormonal milieu remain unknown. The neuropeptide oxytocin has been shown to buffer stress hormone effects on the brain and behavior and may play a role in protecting mPFC structure and function during motherhood. To investigate this, manipulations of oxytocin receptors, cognitive, anxiety, and maternal behavioral assays and measures of structural plasticity will be employed. The results of these studies will inform us ofthe neural and behavioral alterations associated with motherhood and the role that oxytocin may play in these changes. This work serves as the independent portion of the K99/R00 award and will provide the foundation for a research program focused on elucidating the mechanisms of brain resilience.

产后期伴随着激素的急剧变化，包括糖皮质激素的增加 和雌激素水平降低。在处女啮齿动物中，高糖皮质激素和低雌激素水平已被证实 与树突结构减少和树突棘（兴奋性突触位点）减少有关， 内侧前额皮质 (mPFC)。这种荷尔蒙环境也被证明会产生负面影响 mPFC 通过损害认知功能和增强焦虑来介导行为。尽管已知 高糖皮质激素和低雌激素水平的有害影响，具有这种荷尔蒙特征的母亲表现出 减轻焦虑。此外，在 K99 阶段进行的研究表明，树突棘 母鼠 mPFC 的密度增加，这种效应与注意力和注意力的改善相一致。 行为灵活性，功能取决于 mPFC。然而，保护母亲的因素 mPFC 是否来自可能具有破坏性的产后荷尔蒙环境仍然未知。神经肽 催产素已被证明可以缓冲应激激素对大脑和行为的影响，并可能在 在母性期间保护 mPFC 的结构和功能。为了研究这一点，操纵催产素 受体、认知、焦虑和母亲行为分析以及结构可塑性测量将 受雇。这些研究的结果将告诉我们与相关的神经和行为改变 母性以及催产素在这些变化中可能发挥的作用。这部作品作为独立的 K99/R00 奖项的一部分，将为专注于阐明的研究项目提供基础 大脑复原力的机制。