PMID- 18598263
OWN - NLM
STAT- MEDLINE
DCOM- 20081009
LR  - 20231105
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 27
IP  - 12
DP  - 2008 Jun
TI  - Age-related changes in dopamine transporters and accumulation of 3-nitrotyrosine 
      in rhesus monkey midbrain dopamine neurons: relevance in selective neuronal 
      vulnerability to degeneration.
PG  - 3205-15
LID - 10.1111/j.1460-9568.2008.06307.x [doi]
AB  - Aging is the strongest risk factor for developing Parkinson's disease (PD). There 
      is a preferential loss of dopamine (DA) neurons in the ventral tier of the 
      substantia nigra (vtSN) compared to the dorsal tier and ventral tegmental area 
      (VTA) in PD. Examining age-related and region-specific differences in DA neurons 
      represents a means of identifying factors potentially involved in vulnerability 
      or resistance to degeneration. Nitrative stress is among the factors potentially 
      underlying DA neuron degeneration. We studied the relationship between 
      3-nitrotyrosine (3NT; a marker of nitrative damage) and DA transporters [DA 
      transporter (DAT) and vesicular monoamine transporter-2 (VMAT)] during aging in 
      DA subregions of rhesus monkeys. The percentage of DA neurons containing 3NT 
      increased significantly only in the vtSN with advancing age, and the vtSN had a 
      greater percentage of 3NT-positive neurons when compared to the VTA. The 
      relationship between 3NT and DA transporters was determined by measuring 
      fluorescence intensity of 3NT, DAT and VMAT staining. 3NT intensity increased 
      with advancing age in the vtSN. Increased DAT, VMAT and DAT/VMAT ratios were 
      associated with increased 3NT in individual DA neurons. These results suggest 
      nitrative damage accumulates in midbrain DA neurons with advancing age, an effect 
      exacerbated in the vulnerable vtSN. The capacity of a DA neuron to accumulate 
      more cytosolic DA, as inferred from DA transporter expression, is related to 
      accumulation of nitrative damage. These findings are consistent with a role for 
      aging-related accrual of nitrative damage in the selective vulnerability of vtSN 
      neurons to degeneration in PD.
FAU - Kanaan, N M
AU  - Kanaan NM
AD  - Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 
      USA.
FAU - Kordower, J H
AU  - Kordower JH
FAU - Collier, T J
AU  - Collier TJ
LA  - eng
GR  - R01 AG017092/AG/NIA NIH HHS/United States
GR  - AG17092/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Aging/*metabolism/pathology
MH  - Animals
MH  - Cytosol/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Immunohistochemistry
MH  - Macaca mulatta
MH  - Nerve Degeneration/*metabolism/pathology
MH  - Neurons/metabolism/pathology
MH  - Substantia Nigra/*metabolism/pathology
MH  - Tyrosine/*analogs & derivatives/metabolism
MH  - Ventral Tegmental Area/*metabolism/pathology
MH  - Vesicular Monoamine Transport Proteins/metabolism
PMC - PMC3391583
MID - NIHMS384602
EDAT- 2008/07/05 09:00
MHDA- 2008/10/10 09:00
PMCR- 2012/07/08
CRDT- 2008/07/05 09:00
PHST- 2008/07/05 09:00 [pubmed]
PHST- 2008/10/10 09:00 [medline]
PHST- 2008/07/05 09:00 [entrez]
PHST- 2012/07/08 00:00 [pmc-release]
AID - EJN6307 [pii]
AID - 10.1111/j.1460-9568.2008.06307.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2008 Jun;27(12):3205-15. doi: 10.1111/j.1460-9568.2008.06307.x.