Reduction in TrkA-immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome

J Neurochem. 2000 Mar;74(3):1185-96. doi: 10.1046/j.1471-4159.2000.741185.x.

Abstract

Down's syndrome (DS) individuals develop neuropathological features similar to Alzheimer's disease (AD), including degeneration of cholinergic basal forebrain (CBF) neurons. In AD a reduction in CBF/trkA-containing neurons has been suggested to trigger a hyperexpression of galaninergic fibers within the nucleus basalis subfield of the basal forebrain. The present study examined the interrelationship between reductions in CBF/trkA-containing neurons and the overexpression of galaninergic fibers within the nucleus basalis in DS. Within the nucleus basalis stereologic evaluation revealed a 46% reduction in the number of trkA-immunopositive neurons, whereas optical density measurements displayed a nonsignificant 18% reduction in neuronal trkA immunoreactivity in DS as compared with age-matched controls. Western blot analysis also showed a significant reduction in cortical trkA protein levels in DS. A semiquantitative examination of galaninergic fibers in the nucleus basalis revealed only a modest hypertrophy of galaninergic fibers within the nucleus basalis in DS. The present findings indicate a significant reduction in trkA within the nucleus basalis and cortex with only a moderate hypertrophy of galaninergic fibers in DS. These observations suggest that DS may not be an exact genetic model for investigation of changes in the AD basal forebrain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Basal Nucleus of Meynert / metabolism*
  • Basal Nucleus of Meynert / pathology
  • Cerebral Cortex / metabolism
  • Down Syndrome / metabolism*
  • Down Syndrome / pathology
  • Female
  • Galanin / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Nerve Fibers / metabolism*
  • Neurons / metabolism*
  • Prosencephalon / metabolism
  • Receptor, Nerve Growth Factor / metabolism
  • Receptor, trkA / metabolism*
  • Reference Values

Substances

  • Receptor, Nerve Growth Factor
  • Galanin
  • Receptor, trkA