Reduced expression of brain-derived neurotrophic factor protein in Parkinson's disease substantia nigra
Reduced expression of brain-derived neurotrophic factor protein in Parkinson's disease substantia nigra
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DOI：
10.1097/00001756-199902250-00021
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发表时间：
1999-02-25
期刊：
影响因子：
1.7
通讯作者：
Raisman-Vozari, R
中科院分区：
文献类型：
--
作者：
Parain, K;Murer, MG;Raisman-Vozari, R
一些体外和体内研究表明，脑源性神经营养因子(BDNF)促进受损的中脑多巴胺能神经元的存活。我们利用针对重组人BDNF的特异性抗体，在细胞水平上研究了该蛋白在正常对照组和帕金森病(PD)患者死后中脑中的表达。在对照组，BDNF在所有含有多巴胺能神经元的中脑区都有表达，在黑质致密部(SNPC)有65%的黑质神经元表达BDNF。在PD SNPC中，含有BDNF的着色神经元总数减少到相应控制值的9.6%。相反，BDNF非免疫反应阳性的着色神经元的数量减少到相应对照的23.9%。这一结果似乎表明，SNPC黑化神经元不表达BDNF的存活概率是BDNF阳性黑化神经元的2.5倍。此外，我们发现在帕金森病患者的中脑中，几乎所有含有路易体的多巴胺能神经元都呈BDNF免疫反应阳性。这些发现表明BDNF在帕金森病中的表达减少，提示BDNF蛋白的表达不能保护黑化的SNPC神经元免受该病的变性过程的影响。(C)1999年，Lippincott Williams&Wilkins。
SEVERAL in vitro and in vivo studies have shown that brain-derived neurotrophic factor (BDNF) promotes survival of damaged mesencephalic dopaminergic neurons. Using a specific antibody directed against human recombinant BDNF, we studied the expression of the protein at the cellular level in the post-mortem mesencephalon of control subjects and patients with Parkinson's disease (PD). In control subjects, BDNF was expressed in all mesencephalic regions containing dopaminergic neurons, and in the substantia nigra pars compacta (SNpc) 65% of the melanized neurons expressed BDNF. In the PD SNpc, the total number of pigmented neurons containing BDNF was reduced to 9.6% of the corresponding control value. In contrast, the number of pigmented neurons non-immunoreactive for BDNF was reduced to 23.9% of the corresponding control value. This result appears to indicate that SNpc melanized neurons not expressing BDNF have a 2.5-fold greater probability of surviving than BDNF-positive melanized neurons. Furthermore, we found that in parkinsonian mesencephalon almost all dopaminergic neurons containing Lewy bodies were immunoreactive for BDNF. These findings demonstrate a reduced expression of BDNF in PD and suggest that BDNF protein expression does not protect melanized SNpc neurons from the degenerative process in this disease. (C) 1999 Lippincott Williams & Wilkins.