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Dopamine transporter-immunoreactive neurons decrease with age in the human substantia nigra.

S Y Ma1, B J Ciliax, G Stebbins

  • 1Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.

The Journal of Comparative Neurology
|June 11, 1999
PubMed
Summary
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The number of dopamine transporter (DAT) neurons in the substantia nigra significantly decreases with age, with intense DAT neurons declining sharply and light DAT neurons increasing. This age-related neuronal change impacts brain function.

Area of Science:

  • Neuroscience
  • Aging Research
  • Cell Biology

Background:

  • The substantia nigra contains dopaminergic neurons crucial for motor control.
  • Dopamine transporter (DAT) is a key marker for dopaminergic neurons.
  • Age-related changes in neuronal populations can impact brain function.

Purpose of the Study:

  • To quantify age-related changes in dopamine transporter (DAT)-immunoreactive neurons in the human substantia nigra.
  • To investigate the relationship between DAT expression levels and neuronal aging.
  • To establish baseline DAT neuron counts across different age groups.

Main Methods:

  • Unbiased stereologic cell counting was used on human substantia nigra sections.
  • Immunohistochemistry with a monoclonal antibody against DAT was performed.

Related Experiment Videos

  • DAT-immunoreactive neurons were classified into three types based on staining intensity (type 1: intense, type 2: light, type 3: immunonegative).
  • Neuron counts were normalized by calculating the ratio of DAT-containing neurons to neuromelanin-containing cells.
  • Main Results:

    • A significant decrease in intensely stained DAT neurons (type 1) was observed with aging (P < 0.0001).
    • Lightly stained DAT neurons (type 2) and DAT-immunonegative neurons (type 3) increased with age (P < 0.0001 and P < 0.01, respectively).
    • Type 1 neurons decreased by 11.2% per decade, and total nigral neurons decreased by 6.7% per decade.
    • Middle-aged and aged groups showed substantial reductions in type 1 neurons (75% and 88%) compared to the young group.

    Conclusions:

    • There is a significant age-related decline in the number of substantia nigra DAT-immunoreactive neurons, particularly the intensely stained type.
    • The observed shifts in DAT neuron populations suggest complex compensatory mechanisms or neurodegenerative processes during aging.
    • Understanding DAT synthesis regulation may be key to comprehending age-related functional declines associated with DAT changes.