PMID- 14642650
OWN - NLM
STAT- MEDLINE
DCOM- 20040129
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 994
IP  - 2
DP  - 2003 Dec 24
TI  - Injury and strain-dependent dopaminergic neuronal degeneration in the substantia 
      nigra of mice after axotomy or MPTP.
PG  - 243-52
AB  - We studied the effects of axotomy or neurotoxin on the survival of substantia 
      nigra pars compacta (SNpc) neurons in two strains of mice, FVB/N or C57BL/6. 
      Fluoro gold (FG) was injected into both striata of the mice to retrogradely label 
      the nigrostriatal neuronal population. Ten days later, these neurons were 
      axotomized in the medial forebrain bundle (MFB) unilaterally or 
      N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered 
      intraperitonealy for 2 days to produce bilateral degeneration. MFB transection or 
      MPTP administration produced a progressive loss of FG-labeled and tyrosine 
      hydroxylase immunolabeled (TH+) neurons in both strains. Relative to control, 72% 
      of SNpc neurons died 4 weeks after axotomy in C57BL/6 mice and 50% died after 
      axotomy in FVB/N mice. MPTP resulted in death of 80% of SNpc neurons in C57BL/6 
      mice but only 40% in the FVB strain 4 weeks after MPTP administration. In this 
      more sensitive strain, MPTP cell death was associated with positive staining for 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and 
      nuclear condensation. In contrast, no TUNEL staining was detected in SNpc after 
      MPTP in FVB/N mice. Further, while similar kinetics and extent of cell death 
      accompanied axotomy, axotomy-induced cell death was TUNEL negative in both FVB/N 
      and C57BL/6 mice. Double staining for TUNEL and microtubule associated protein 2 
      confirmed that the majority of the TUNEL positive cells were neurons. These data 
      indicate that genetic factors and the type of lesion play an important role in 
      determining death of dopaminergic neurons after injury.
FAU - Liu, Li
AU  - Liu L
AD  - Division of Applied and Interventional Research, Toronto Western Hospital 
      Research Institute, University of Toronto, 399 Bathurst Street, Toronto ON, 
      Canada, M5T 2S8.
FAU - Hsu, Shu S
AU  - Hsu SS
FAU - Kalia, Suneil K
AU  - Kalia SK
FAU - Lozano, Andres M
AU  - Lozano AM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt)
RN  - 0 (Dopamine Agents)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Stilbamidines)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - *1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MH  - Animals
MH  - *Axotomy/methods
MH  - Cell Count
MH  - Cell Death/drug effects
MH  - Dopamine/*metabolism
MH  - Dopamine Agents
MH  - Female
MH  - Fluorescent Dyes/metabolism
MH  - Functional Laterality
MH  - In Situ Nick-End Labeling/methods
MH  - Medial Forebrain Bundle/injuries
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microtubule-Associated Proteins/metabolism
MH  - Nerve Degeneration/chemically induced/*metabolism
MH  - Stilbamidines/metabolism
MH  - Substantia Nigra/pathology/*surgery
MH  - Time Factors
MH  - Tyrosine 3-Monooxygenase/metabolism
EDAT- 2003/12/04 05:00
MHDA- 2004/01/30 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/01/30 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - S0006899303037958 [pii]
AID - 10.1016/j.brainres.2003.09.066 [doi]
PST - ppublish
SO  - Brain Res. 2003 Dec 24;994(2):243-52. doi: 10.1016/j.brainres.2003.09.066.