Fetal Microchimerism in the Human Brain

项目摘要/摘要 微嵌合体(Mc)指的是拥有少量细胞或来自基因不同个体的DNA。 在母子身体结合结束许多年后，在母亲和母亲的Mc中发现了胎儿Mc 是在她的后代身上发现的。已在儿童和成人中发现了胎儿Mc和母体Mc，在血液和 器官包括心、肝、脾、肾和胰腺。尽管大脑对人类很重要 健康和功能人类大脑中存在着Mc的基本知识鸿沟。人类的大脑是 可能在女性体内含有胎儿Mc，在她的后代中含有母体Mc，这是最近的实验支持的 在这些研究中，在母鼠脑中发现了胎儿Mc，在胎鼠脑中发现了母体Mc。 此外，在实验和人体研究中，Mc似乎具有区分创造的能力， 例如，心脏中的心肌细胞、胰腺中的胰岛b细胞和肝脏中的肝细胞。研究项目： 这项提议将首次识别和表征自然获得的胎儿Mc和母体Mc 人脑。为了建立基本的初步知识，胎儿Mc的患病率、数量和细胞表型将 根据不同的年龄和特定的大脑区域确定。建立有关以下内容的初始信息 手术切除的母体脑标本将用于研究药物难治性患者 家庭成员参与的癫痫。在这些研究中，孕妇的Mc将通过以下方式进行专门的测定 人类白细胞抗原和其他多态特异性定量聚合酶链式反应(QPCR)。所有家庭成员的参与将允许 进一步评估其他潜在的Mc来源，包括来自较年长的兄弟姐妹的，由母亲传递给 下一次怀孕的胎儿，或消失的双胞胎。Mc可以影响人脑的方式有 多样性和多样性，既对个人有利，也对个人不利。如果自然获得的Mc是一个基本的 在生物学方面，正如我们假设的那样，拟议的工作将建立一个基础，从 可以研究人类大脑的疾病，包括自身免疫、肿瘤、发育和 退化的条件。

PROJECT SUMMARY/ABSTRACT Microchimerism (Mc) refers to harboring a small amount of cells or DNA from a genetically distinct individual. Many years after the physical union of mother and child ends fetal Mc is found in the mother and maternal Mc is found in her progeny. Fetal Mc and maternal Mc have been identified in children and adults, in blood and organs including heart, liver, spleen, kidney and pancreas. Despite the importance of the brain to human health and function a fundamental gap in knowledge exists for Mc in the human brain. That human brain is likely to contain fetal Mc in women and maternal Mc in her progeny is supported by recent experimental studies in which fetal Mc was identified in the maternal mouse brain and maternal Mc in the fetal mouse brain. Moreover, in experimental and human studies Mc appears to have the capacity to differentiate creating, for example, cardiac myocytes in the heart, islet b cells in the pancreas and hepatocytes in the liver. Studies in this proposal will for the first time identify and characterize naturally acquired fetal Mc and maternal Mc in the human brain. To establish fundamental initial knowledge fetal Mc prevalence, quantity and cell phenotypes will be determined across age and according to specific brain regions. To establish initial information about maternal Mc surgically excised brain specimens will be studied from patients with medication refractory epilepsy for whom family members participate. In these studies maternal Mc will be specifically assayed by HLA and other polymorphism specific quantitative PCR (qPCR). Participation of all family members will permit further evaluation for other potential Mc sources including from an older sibling, passed by the mother to the fetus of a subsequent pregnancy, or a vanished twin. The ways in which Mc could affect the human brain are multiple and diverse, both to the benefit and detriment of the individual. If naturally acquired Mc is a basic aspect of biology as we hypothesize, the proposed work will have created a foundation from which diverse disorders of the human brain can be investigated, including autoimmune, neoplastic, developmental and degenerative conditions.