PMID- 11429269 OWN - NLM STAT- MEDLINE DCOM- 20010823 LR - 20191104 IS - 0891-0618 (Print) IS - 0891-0618 (Linking) VI - 21 IP - 4 DP - 2001 Jun TI - Depletion of glial cell line-derived neurotrophic factor in substantia nigra neurons of Parkinson's disease brain. PG - 277-88 AB - 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-4 (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. FAU - Chauhan, N B AU - Chauhan NB AD - Research and Development Service, Edward Hines, Jr., Veterans Affairs Hospital, Hines, IL 60141, USA. FAU - Siegel, G J AU - Siegel GJ FAU - Lee, J M AU - Lee JM LA - eng PT - Journal Article PL - Netherlands TA - J Chem Neuroanat JT - Journal of chemical neuroanatomy JID - 8902615 RN - 0 (GDNF protein, human) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) SB - IM MH - Aged MH - Blotting, Western MH - Glial Cell Line-Derived Neurotrophic Factor MH - Humans MH - Image Processing, Computer-Assisted MH - Immunohistochemistry MH - Male MH - Mesencephalon/metabolism MH - Nerve Growth Factors/*metabolism MH - Nerve Tissue Proteins/*metabolism MH - Parkinson Disease/*metabolism/pathology MH - Substantia Nigra/*cytology/*metabolism EDAT- 2001/06/29 10:00 MHDA- 2001/08/24 10:01 CRDT- 2001/06/29 10:00 PHST- 2001/06/29 10:00 [pubmed] PHST- 2001/08/24 10:01 [medline] PHST- 2001/06/29 10:00 [entrez] AID - S0891061801001156 [pii] AID - 10.1016/s0891-0618(01)00115-6 [doi] PST - ppublish SO - J Chem Neuroanat. 2001 Jun;21(4):277-88. doi: 10.1016/s0891-0618(01)00115-6.