title: Presence of proNGF-sortilin signaling complex in nigral dopamine neurons and its variation in relation to aging, lactacystin and 6-OHDA insults.
abstract: Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a crucial factor in neurodegeneration, but it remains unclear if it may function in nigral neurons under aging and disease. The purpose of this study is to examine and quantify proNGF and sortilin expression in the substantia nigra and dynamic changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease using immunofluorescence, electronic microscopy, western blot and FLIVO staining methods. The expression of proNGF and sortilin was abundantly and selectively identified in tyrosine hydroxylase (TH)-containing dopamine neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons were densely distributed in the ventral tier, while they were less distributed in the dorsal tier, where calbindin-D28K-containing neurons were numerously located. A correlated decrease of proNGF, sortilin and TH was also detected during animal aging process. While increase of proNGF, sortilin and cleaved (active) caspase-3 expression was found in the lactacystin model, dynamic proNGF and sortilin changes along with dopamine neuronal loss were demonstrated in the substantia nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and its response to aging, lactacystin and 6-OHDA insults, suggesting that it might contribute to neuronal apoptosis or neurodegeneration during pathogenesis and disease progression of Parkinson's disease; the underlying mechanism and key signaling pathways involved warrant further investigation.
authors.affiliation: Institute of Neurosciences, Fourth Military Medical University, Xi'an 710032, China. shylockk-xy@hotmail.com
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Bei-Yu
authors.initials: BY
authors.lastname: Chen
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Duan
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Gao
authors.forename: Jing-Jie
authors.initials: JJ
authors.lastname: Wang
authors.forename: Ken Kam-Lin
authors.initials: KK
authors.lastname: Yung
authors.forename: Liang-Wei
authors.initials: LW
authors.lastname: Chen
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000375:Aging; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D016627:Oxidopamine / Q000633:toxicity*; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099183:Sortilin
chemical_list: D000111:Acetylcysteine; D033942:Adaptor Proteins, Vesicular Transport; D000900:Anti-Bacterial Agents; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D011498:Protein Precursors; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D000099183:Sortilin; C067713:lactacystin; C068313:Ngfr protein, rat