Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson's disease brain

被引:181
作者
Chauhan, NB
Siegel, GJ [1 ]
Lee, JM
机构
[1] Vet Affairs Edward Hines Jr Hosp, Neurol Serv 127, Hines, IL 60141 USA
[2] Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA
[3] Loyola Univ, Stritch Sch Med, Dept Neurol, Maywood, IL 60153 USA
[4] Loyola Univ, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60141 USA
[5] Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60141 USA
[6] Loyola Univ, Stritch Sch Med, Dept Pharmacol & Expt Therapeut, Maywood, IL 60141 USA
关键词
aging; dopaminergic neurons; image analysis; immunocytochemistry; neuronal loss; neurotrophic factors; Parkinson's disease; substantia nigra;
D O I
10.1016/S0891-0618(01)00115-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The distribution of nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-il (NT-4) in substantia nigra pars compacta (SNc) of Parkinson's disease (PD) brains was investigated by immunofluorescence. Cases studied included four 69-77 year old neurologically normal male controls and four 72-79 year old male PD patients. Integrated optical densities (IODs) of immunofluorescence over individual neuromelanin-containing neurons and in areas of neuropil and the number of neurons on H & E stained adjacent sections were quantitated with the use of the BioQuant Image Analyzer. Data were statistically analyzed by ANOVA, including the unpaired two-tailed Student t-test and the Mann-Whitney test. The results showed 55.8% (P < 0.0001) dropout of SNc neurons in PD brains compared to age-matched controls. Despite considerable neuronal dropout, immunofluorescent NTFs in the PD brains showed differential reductions that were consistent within the group as compared to age-matched controls: reductions were GDNF, 19.4%/neuron (P < 0.0001), 20.2%/neuropil (P < 0.0001); CNTF 11.1%/neuron (P < 0.0001), 9.4%/neuropil (P < 0.0001): BDNF, 8.6%/neuron (P < 0.0001), 2.5%/neuropil. NGF, NT-3 and NT-4 showed no significant differences within surviving neurons or neuropil. Since the depletion of GDNF both within surviving neurons and neuropil was twice as great as that of CNTF and BDNF and since the other NTFs showed no changes, GDNF, of the tested NTFs, is probably the most susceptible and the earliest to decrease in the surviving neurons of SNc. These observations suggest a role for decreased availability of GDNF in the process of SNc neurodegeneration in PD. (C) 2001 Elsevier Science B.V. All rights reserved.
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页码:277 / 288
页数:12
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