Brain LC-PUFAs and Maternal Mental Health

大脑 LC-PUFA 与孕产妇心理健康

• 批准号: 6812717
• 负责人: BETH LEVANT
• 金额: $ 24.38万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6812717
• 关键词: brain derived neurotrophic factor; brain metabolism; corticotropin releasing factor; dietary lipid; fatty acid biosynthesis; female; hippocampus; hypothalamic pituitary adrenal axis; laboratory rat; lactation; maternal behavior; neurochemistry; neuroregulation; nutrition related tag; omega 3 fatty acid; postpartum depression; pregnancy; unsaturated fatty acids

DESCRIPTION (provided by applicant): Alterations in brain long-chain polyunsaturated fatty acid (LC-PUFA) composition, particularly decreased docosahexaenoic acid (DHA), are implicated as a contributing factor in depression and psychosis. Our preliminary data indicates that pregnancy and lactation can deplete the maternal brain of DHA. Accordingly, these studies are designed to test the HYPOTHESIS that depletion of maternal brain DHA during pregnancy and lactation contributes to postpartum mental illness. The Specific Aims will use a rat model to: 1. Determine the effects of pregnancy and lactation on levels of maternal brain DHA and other LC-PUFA. Manipulation of dietary fatty acid content will be used to alter maternal brain DHA levels. LC-PUFA will be assessed in four brain regions associated with depression and psychosis, as well as in erythrocytes. These studies will establish a rodent model with which to study the effects of depleted brain DHA levels following pregnancy and lactation on neurochemical parameters associated with depression and psychosis in humans. 2. Determine the effects of reduced brain DHA in the postpartum period on maternal hypothalamic-pituitary-adrenal (HPA) axis activity and regulation. Regulation of the HPA axis will be assessed using a modification of the dexamethasone suppression test. The affinity and density of cerebral cortical corticotrophin releasing factor1 (CRF1) receptors will also be quantified. 3. Determine the effects of reduced brain DHA in the postpartum period on monoamine neurochemistry. The concentrations of serotonin, norepinephrine, and dopamine (and their respective metabolites) will be measured in brain regions relevant to depression or psychosis. The affinity and density of receptors most strongly implicated in depression or psychosis (5-HT1A, 5-TH2A, beta, D2, and D3) will also be quantified. 4. Determine the effects of reduced brain DHA in the postpartum period on expression of brain-derived neurotrophic factor (BDNF) in hippocampus. Hippocampal expression of the BDNF gene, which is decreased in animal models of depression, will be measured by RNAse protectionassay. These experiments will determine whether reproductive activity and the resulting alterations in maternal brain LC-PUFA content are likely to contribute to postpartum mental illness in women. Findings will point to causes of postpartum mental illness and thus the identification of women at risk and the elimination of risk factors. These findings will also suggest novel treatments for such illnesses when they occur.

描述（由申请人提供）：大脑长链多不饱和脂肪酸（LC-PUFA）组成的改变，尤其是Docosahexaenoic酸（DHA）的降低，涉及到抑郁症和精神病的促成因素。我们的初步数据表明，妊娠和泌乳会耗尽DHA的母亲大脑。因此，这些研究旨在检验以下假设：孕妇在怀孕期间和泌乳期间的耗尽会导致产后精神疾病。具体目的将使用大鼠模型来： 1。确定妊娠和泌乳对母性脑DHA和其他LC-PUFA水平的影响。饮食脂肪酸含量的操纵将用于改变母体脑DHA水平。 LC-PUFA将在与抑郁和精神病以及红细胞相关的四个大脑区域进行评估。这些研究将建立一个啮齿动物模型，以研究妊娠后耗尽的脑DHA水平的影响以及泌乳对与人类抑郁症和精神病相关的神经化学参数的影响。 2。确定产后减少脑DHA对母体下丘脑 - 垂体 - 肾上腺（HPA）轴活动和调节的影响。将使用地塞米松抑制测试的修改来评估HPA轴的调节。还将定量脑皮质性皮质营养素释放因子1（CRF1）受体的亲和力和密度。 3。确定产后减少脑DHA对单胺神经化学的影响。 5-羟色胺，去甲肾上腺素和多巴胺（及其各自代谢产物）的浓度将在与抑郁症或精神病有关的大脑区域中进行测量。受体的亲和力和密度最强烈地涉及抑郁症或精神病（5-HT1A，5-TH2A，BETA，D2和D3）也将被量化。 4。确定产后减少脑DHA对海马中脑衍生神经营养因子（BDNF）表达的影响。 BDNF基因的海马表达在抑郁症的动物模型中降低，将通过RNase ProtectionAssay进行测量。 这些实验将确定生殖活性以及产妇大脑LC-PUFA含量的改变是否可能导致女性产后精神疾病。调查结果将指出产后精神疾病的原因，从而确定处于危险中的妇女和消除危险因素。这些发现还会在发生这种疾病时提出新的治疗方法。