PMID- 11054705
OWN - NLM
STAT- MEDLINE
DCOM- 20010104
LR  - 20190906
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 427
IP  - 3
DP  - 2000 Nov 20
TI  - Time course of degenerative alterations in nigral dopaminergic neurons following 
      a 6-hydroxydopamine lesion.
PG  - 440-54
AB  - The neurotoxin 6-hydroxydopamine (6-OHDA) has been used extensively in animal 
      models of Parkinson's disease. Typically, rodents develop severe unilateral 
      movement deficiencies coupled with apomorphine-induced rotation behavior at least 
      1 week after an ipsilateral 6-OHDA lesion of the nigrostriatal dopamine (DA) 
      system. The short-term morphological effects of 6-OHDA have not been determined 
      in detail, however, and the exact process by which neurons die has not been 
      elucidated. Thus, novel degenerative markers were used to determine the temporal 
      pattern of acute phenotypic and degenerative alterations following a unilateral 
      6-OHDA injection into the medial forebrain bundle of adult rats. 
      6-Hydroxydopamine administration resulted in an increase in terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining as 
      early as 6 hours postlesion. Staining for FluoroJade, a marker of neuronal 
      degeneration, was evident at all time points examined but was maximal at 48 
      hours. Loss of tyrosine hydroxylase (TH) immunoreactivity began in axons at 6 
      hours, and progressed to cell bodies at later time points postlesion. 
      Morphological examination of these neurons supported the conclusion of their 
      death via apoptosis. Thus, whereas behavioral manifestations typically become 
      evident 1 week or more following a 6-OHDA lesion, it is evident that nigral cell 
      degeneration begins much earlier. This suggests multiple therapeutic 
      possibilities, including the prevention of apoptosis, in affected neurons.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Zuch, C L
AU  - Zuch CL
AD  - Department of Pharmacology, University of Colorado Health Sciences Center, 
      Denver, Colorado 80262, USA.
FAU - Nordstroem, V K
AU  - Nordstroem VK
FAU - Briedrick, L A
AU  - Briedrick LA
FAU - Hoernig, G R
AU  - Hoernig GR
FAU - Granholm, A C
AU  - Granholm AC
FAU - Bickford, P C
AU  - Bickford PC
LA  - eng
GR  - AG12122/AG/NIA NIH HHS/United States
GR  - AG15239/AG/NIA NIH HHS/United States
GR  - NS10851/NS/NINDS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Comp Neurol
JT  - The Journal of comparative neurology
JID - 0406041
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Sympatholytics)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Death
MH  - Dopamine/physiology
MH  - Fluorescent Dyes
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Longitudinal Studies
MH  - Male
MH  - Nerve Degeneration/chemically induced/*pathology
MH  - Neurons/enzymology/pathology
MH  - *Oxidopamine
MH  - Parkinsonian Disorders/chemically induced/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substantia Nigra/*pathology
MH  - *Sympatholytics
MH  - Tyrosine 3-Monooxygenase/analysis
EDAT- 2000/10/31 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/31 11:00
PHST- 2000/10/31 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/31 11:00 [entrez]
AID - 10.1002/1096-9861(20001120)427:3<440::AID-CNE10>3.0.CO;2-7 [pii]
AID - 10.1002/1096-9861(20001120)427:3<440::aid-cne10>3.0.co;2-7 [doi]
PST - ppublish
SO  - J Comp Neurol. 2000 Nov 20;427(3):440-54. doi: 
      10.1002/1096-9861(20001120)427:3<440::aid-cne10>3.0.co;2-7.