Decreased plasma membrane expression of striatal dopamine transporter in aging

Michael Francis Salvatore, Subbu Apparsundaram, Greg A. Gerhardt

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Abstract

Aging in rodents, monkeys, and man is correlated with a reduction in dopamine transporter (DAT) ligand binding and DAT function. Using Western blot techniques, we investigated whether the source of these age-related changes in DAT was correlated with decreases in DAT protein levels in the striatum, substantia nigra (SN), nucleus accumbens (NAc), and ventral tegmental area (VTA) of 6, 18, and 24-month-old male Fischer 344 rats. The relative levels of tyrosine hydroxylase (TH) were also determined in each region. In the striatum, we also assessed [3H]-DA uptake and DAT plasma membrane expression using a membrane-impermeant biotin analog in crude synaptosomes prepared from these age groups. There was no significant age-related difference in DAT immunoreactivity per total protein or per total TH in striatum, NAc, SN, or VTA. Significant age-related changes in TH were only seen in the VTA of the 24-month-old rats (~60% decrease). However, [3H]-DA uptake and DAT protein recovered in the biotinylated fraction in 24-month-old rats were significantly decreased (~30%) compared to 6-month-old animals in the striatal synaptosomes. These data suggest that age-related decreases in striatal DAT function and ligand binding are related to a decrease in plasma membrane expression of DAT and not a decrease in the steady-state levels of DAT protein or loss of dopaminergic neuropil.

Original languageEnglish
Pages (from-to)1147-1154
Number of pages8
JournalNeurobiology of Aging
Volume24
Issue number8
DOIs
StatePublished - 1 Jan 2003

Fingerprint

Corpus Striatum
Dopamine Plasma Membrane Transport Proteins
Cell Membrane
Ventral Tegmental Area
Tyrosine 3-Monooxygenase
Synaptosomes
Nucleus Accumbens
Substantia Nigra
Ligands
Neuropil
Inbred F344 Rats
Biotin
Haplorhini
Rodentia
Age Groups
Western Blotting

Keywords

  • Aging
  • Dopamine transporter
  • Mesolimbic
  • Nigrostriatal
  • Nucleus accumbens
  • Striatum
  • Tyrosine hydroxylase

Cite this

Salvatore, Michael Francis ; Apparsundaram, Subbu ; Gerhardt, Greg A. / Decreased plasma membrane expression of striatal dopamine transporter in aging. In: Neurobiology of Aging. 2003 ; Vol. 24, No. 8. pp. 1147-1154.
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Decreased plasma membrane expression of striatal dopamine transporter in aging. / Salvatore, Michael Francis; Apparsundaram, Subbu; Gerhardt, Greg A.

In: Neurobiology of Aging, Vol. 24, No. 8, 01.01.2003, p. 1147-1154.

Research output: Contribution to journalArticleResearchpeer-review

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