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神经生长因子剥夺的实验性自身免疫模型:对发育中的外周交感和感觉神经元的影响

Experimental autoimmune model of nerve growth factor deprivation: effects on developing peripheral sympathetic and sensory neurons.

作者信息

Gorin P D, Johnson E M

出版信息

Proc Natl Acad Sci U S A. 1979 Oct;76(10):5382-6. doi: 10.1073/pnas.76.10.5382.

DOI:10.1073/pnas.76.10.5382
PMID:92024
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC413147/
Abstract

An experimental autoimmune model of nerve growth factor (NGF) deprivation has been used to assess the role of NGF in the development of various cell types in the nervous system. Adult rats immunized with 2.5S mouse NGF in complete Freund's adjuvant produced antibodies that crossreacted with their own NGF and that were transferred in utero to the fetus and in milk to the neonate. Cross-fostering experiments were carried out to separate the effects of exposure to anti-NGF in utero from those due to exposure through the milk. Anti-NGF transferred in utero and in milk resulted in the destruction of peripheral sympathetic neurons assessed by morphological methods (light microscopy) and biochemical methods (tyrosine hydroxylase activity, choline acetyltransferase activity, and protein content). No effects were observed on the adrenal medulla. Offspring of NGF-immunized females exposed to anti-NGF in utero had a decreased protein content in the dorsal root ganglia and were unable to transport (125)I-labeled NGF injected in the forepaw to the dorsal root ganglia. These results suggest that a subpopulation of sensory neurons is dependent on NGF for survival during some period of fetal development. This model offers the potential for determining the degree and time of dependence of various cell types on NGF.

摘要

一种神经生长因子(NGF)剥夺的实验性自身免疫模型已被用于评估NGF在神经系统中各种细胞类型发育中的作用。用2.5S小鼠NGF与完全弗氏佐剂免疫成年大鼠,产生的抗体与它们自身的NGF发生交叉反应,并在子宫内传递给胎儿,在乳汁中传递给新生儿。进行了交叉寄养实验,以区分子宫内接触抗NGF的影响与通过乳汁接触抗NGF的影响。子宫内和乳汁中传递的抗NGF导致外周交感神经元的破坏,这通过形态学方法(光学显微镜)和生化方法(酪氨酸羟化酶活性、胆碱乙酰转移酶活性和蛋白质含量)进行评估。对肾上腺髓质未观察到影响。子宫内接触抗NGF的NGF免疫雌性后代的背根神经节蛋白质含量降低,并且无法将注射在前爪的(125)I标记的NGF转运至背根神经节。这些结果表明,在胎儿发育的某个时期,一部分感觉神经元的存活依赖于NGF。该模型为确定各种细胞类型对NGF的依赖程度和时间提供了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc80/413147/981c5a8975dd/pnas00010-0643-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc80/413147/981c5a8975dd/pnas00010-0643-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc80/413147/981c5a8975dd/pnas00010-0643-a.jpg

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本文引用的文献

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封面故事:评价靶向神经生长因子的单克隆抗体替扎奴单抗对成年食蟹猴(Macaca fascicularis)交感神经系统的影响:体视学、组织形态学和心功能评估。
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DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity.DLK 通过选择性调节促凋亡 JNK 活性诱导发育性神经元变性。
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Potential mechanisms for hypoalgesia induced by anti-nerve growth factor immunoglobulin are identified using autoimmune nerve growth factor deprivation.使用自身免疫性神经生长因子剥夺的方法,确定了抗神经生长因子免疫球蛋白诱导的镇痛作用的潜在机制。
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