Motherhood, Oxytocin and the Medial Prefrontal Cortex

描述（由申请人提供）：产后期间伴有剧烈的内分泌和行为改变。这些变化包括基础糖皮质激素水平升高和雌激素水平降低。糖皮质激素升高和雌激素水平降低与成年雄性和雌性啮齿动物的认知障碍和焦虑增强有关，然而，大多数产后雌性啮齿动物没有表现出这些负面结果。由于母性也与催产素（OT）的升高有关，催产素是一种神经肽，已被证明可以缓冲应激激素对大脑和身体的影响，因此催产素有可能保护孕妇免受潜在的产后激素环境的伤害。内侧前额叶皮层（mPFC）是一个与情绪障碍、认知行为和产妇护理有关的大脑区域。mPFC对激素也很敏感——雌激素和糖皮质激素都会改变mPFC的树突结构和树突棘，即兴奋性突触的位置。在Elizabeth Gould教授实验室的指导阶段，我将研究产后mPFC的结构是否能抵抗产后有害的激素环境，以及这些变化是否构成mPFC依赖行为的基础。这项工作将为该奖项的独立阶段奠定基础，该阶段将包括检查mPFC中的OT是否在产后期间调节结构和/或行为弹性。这项研究的直接目标是阐明母性对mPFC结构和功能的影响，更广泛的目标是获得一个教职，在那里我可以继续确定母亲大脑弹性的因素和机制，作为一个独立的科学家。相关性：对许多女性来说，成为母亲是人类最重要、最有意义的经历之一。然而，在产后期间发生的剧烈荷尔蒙变化可能使一些新妈妈对养育子女的要求反应消极。事实上，据估计，10-15%的新妈妈会经历产后抑郁和/或焦虑。由于mPFC和OT与产妇护理和情绪障碍有关，了解母性和OT引起的mPFC结构改变及其行为后果可能有助于深入了解精神疾病易感性和抵抗力的潜在机制。

DESCRIPTION (provided by applicant): The postpartum period is accompanied by dramatic endocrine and behavioral alterations. Among these changes are increased basal glucocorticoid levels and decreased estrogen levels. Elevated glucocorticoid and diminished estrogen levels have been associated with cognitive impairment and enhanced anxiety in adult virgin male and female rodents and yet, the majority of postpartum females do not exhibit these negative outcomes. Since motherhood is also associated with elevations in oxytocin (OT), a neuropeptide that has been shown to buffer stress hormone effects on the brain and body, it's possible that OT protects against the potentially damaging postpartum hormonal milieu. The medial prefrontal cortex (mPFC) is a brain region that has been linked to mood disorders, cognitive behavior and maternal care. The mPFC is also sensitive to hormones - both estrogen and glucocorticoids alter dendritic architecture and dendritic spines, sites of excitatory synapses, in the mPFC. During the mentored phase of the award in the laboratory of Prof. Elizabeth Gould, I will investigate whether the structure of the postpartum mPFC is resistant to the detrimental postpartum hormonal environment and whether these changes underlie mPFC dependent behaviors. This work will set the stage for the independent phase of the award which will involve examining whether OT in the mPFC mediates structural and/or behavioral resilience during the postpartum period. The immediate goal of this research is to elucidate the effects of motherhood on mPFC structure and function with the broader objective of obtaining a faculty position where I can continue to identify the factors and mechanisms which underlie resilience of the maternal brain as an independent scientist. Relevance: For many women, becoming a mother is one of the most significant and rewarding human experiences. However, the dramatic hormonal changes that occur during the postpartum period may predispose some new mothers to react negatively to the demands of parenting. Indeed, it is estimated that 10-15% of new mothers experience postpartum depression and/or anxiety. Since the mPFC and OT have been linked to maternal care and mood disorders, understanding motherhood and OT induced structural alterations of the mPFC and their behavioral consequences may provide insight into the mechanisms underlying predisposition and resistance to mental illness.