Overexpression of tumour necrosis factor α in the brain of transgenic mice differentially alters nerve growth factor levels and choline acetyltransferase activity
Overexpression of tumour necrosis factor α in the brain of transgenic mice differentially alters nerve growth factor levels and choline acetyltransferase activity
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DOI：
10.1006/cyto.1998.0397
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发表时间：
1999-01-01
期刊：
影响因子：
3.8
通讯作者：
Tirassa, P
中科院分区：
文献类型：
--
作者：
Aloe, L;Fiore, M;Tirassa, P
肿瘤坏死因子α（TNF-α）是一种主要由巨噬细胞和单核细胞合成的多效性细胞因子，其在炎症反应、免疫反应和伤口愈合期间发挥多种生物活性。在中枢神经系统（CNS）内，TNF-α的基础水平几乎检测不到，但在神经损伤后会增加。使用在CNS中表达高水平TNF-α的转基因小鼠，我们研究了这种细胞因子对脑神经生长因子（NGF）水平的影响，NGF是一种神经营养因子，在基底前脑胆碱能神经元的发育、维持和再生中起着至关重要的作用。免疫酶法和原位杂交结果显示，NGF在海马的组成性表达减少，在下丘脑的表达增加，而在皮层的表达无明显变化。此外，隔胆碱能神经元接受营养支持的神经生长因子在海马显示胆碱乙酰转移酶免疫反应性的损失，这表明，减少可用性的神经生长因子可能会产生负面影响脑胆碱能神经元的合成。这些观察结果表明，脑神经生长因子的基础水平可以受到TNF-α的局部表达的负面或正面影响，并且这种细胞因子通过剂量依赖性调节神经生长因子的合成和释放，可能参与与衰老相关的神经退行性事件。(C)北京：科学出版社.
Tumour necrosis factor at (TNF-alpha) is a pleiotrophic cytokine synthesized primarily by macrophages and monocytes, which exerts a variety of biological activities during inflammatory responses, immune reactions, and wound healing. Within the central nervous system (CNS), the basal levels of TNF-alpha are almost undetectable, but increase after neurological insults. Using transgenic mice expressing high levels of TNF-alpha in the CNS, we investigated the effect of this cytokine on the levels of brain nerve growth factor (NGF), a neurotrophin playing a crucial role in the development, maintenance and regeneration of basal forebrain cholinergic neurons. The immunoenzymatic assay and in situ hybridization revealed that the constitutive expression of NGF decreased in the hippocampus, increased in the hypothalamus, while remained unchanged in the cortex. Moreover, septal cholinergic neurons which receive trophic support from NGF produced in the hippocampus display loss of choline acetyltransferase immunoreactivity, suggesting that the reduced availability of NGF may influence negatively the synthesis of brain cholinergic neurons. These observations indicate that the basal level of brain NGF can be influenced negatively or positively by local expression of TNF-alpha and that this cytokine, through dose-dependent regulation of NGF synthesis and release, may be involved in neurodegenerative events associated with aging. (C) 1999 Academic Press.