Fetal Microchimerism in the Human Brain

描述（由申请人提供）：微嵌合（Mc）是指从遗传上不同的个体中容纳少量细胞或DNA。在母亲和孩子的身体结合结束多年后，在母亲身上发现了胎儿的Mc，在她的后代身上发现了母体的Mc。在儿童和成人、血液和心脏、肝脏、脾脏、肾脏和胰腺等器官中都发现了胎儿和母体的Mc。尽管大脑对人类健康和功能的重要性，但在人类大脑中存在着基本的知识空白。最近的实验研究证实，女性大脑中可能含有胎儿Mc，而其后代中可能含有母体Mc。这些实验研究在母鼠大脑中发现了胎儿Mc，而母鼠大脑中也发现了母体Mc。此外，在实验和人体研究中，Mc似乎具有分化的能力，例如，在心脏中产生心肌细胞，在胰腺中产生胰岛b细胞和在肝脏中产生肝细胞。本研究将首次鉴定和表征人类大脑中自然获得的胎儿和母体Mc。为了建立基本的初步知识，胎儿Mc患病率，数量和细胞表型将根据年龄和特定的大脑区域确定。为了确定母体Mc手术切除的脑标本的初步信息，将对有家庭成员参与的药物难治性癫痫患者进行研究。在这些研究中，母体Mc将通过HLA和其他多态性特异性定量PCR （qPCR）进行特异性检测。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，包括从一个年长的兄弟姐妹，由母亲传递给随后怀孕的胎儿，或一个消失的双胞胎。Mc影响人类大脑的方式多种多样，对个人既有好处也有坏处。如果像我们假设的那样，自然获得的Mc是生物学的一个基本方面，那么这项工作将为研究人类大脑的各种疾病奠定基础，包括自身免疫、肿瘤、发育和退行性疾病。

DESCRIPTION (provided by applicant): 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 fo 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. PUBLIC HEALTH RELEVANCE: Some cells traffic in both directions between a mother and fetus during pregnancy and surprisingly, small numbers of cells from the fetus persist in the mother, and from the mother in her children, including into adult life. These cells are likely to have both beneficial and adverse effects. A healthy brain is important to human functioning and studies in this proposal will investigate these naturally acquired fetal and maternal cells for the first time in the human brain.