Brain LC-PUFAs and Maternal Mental Health

大脑 LC-PUFA 与孕产妇心理健康

• 批准号: 6949129
• 负责人: BETH LEVANT
• 金额: $ 22.05万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949129
• 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）：脑长链多不饱和脂肪酸（LC-PUFA）组成的改变，特别是二十二碳六烯酸（DHA）减少，是抑郁症和精神病的一个促成因素。我们的初步数据表明，怀孕和哺乳会消耗母亲大脑中的DHA。因此，这些研究旨在验证怀孕和哺乳期间母亲大脑DHA消耗导致产后精神疾病的假设。特定目标将使用大鼠模型： 1.确定怀孕和哺乳对母体大脑DHA和其他LC-PUFA水平的影响。控制膳食脂肪酸含量将用于改变母体大脑DHA水平。LC-PUFA将在与抑郁症和精神病相关的四个大脑区域以及红细胞中进行评估。这些研究将建立啮齿动物模型，用于研究妊娠和哺乳后大脑DHA水平耗尽对人类抑郁症和精神病相关神经化学参数的影响。 2.确定产后期间大脑DHA减少对母体下丘脑-垂体-肾上腺（HPA）轴活动和调节的影响。将使用地塞米松抑制试验的改良评估HPA轴的调节。还将定量大脑皮质促肾上腺皮质激素释放因子1（CRF 1）受体的亲和力和密度。 3.确定产后期间大脑DHA减少对单胺神经化学的影响。将在与抑郁症或精神病相关的脑区测量血清素、去甲肾上腺素和多巴胺（及其各自的代谢物）的浓度。还将定量与抑郁症或精神病最密切相关的受体（5-HT 1A、5-TH 2A、β、D2和D3）的亲和力和密度。 4.确定产后期间脑DHA减少对海马中脑源性神经营养因子（BDNF）表达的影响。在抑郁症动物模型中，BDNF基因的海马表达降低，将通过RNA酶保护试验来测量。 这些实验将确定生殖活动和由此产生的母体大脑LC-PUFA含量的变化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，从而确定有风险的妇女和消除风险因素。这些发现还将为此类疾病的发生提供新的治疗方法。