Glial-neurotrophic mechanisms in Down syndrome

  • P. G. Nelson
  • S. K. McCune
  • A. M. Ades
  • K. B. Nelson


Complex interactions and interconnectivity between neurons are hallmarks of normal neuronal differentiation and development. Neurons also interact with other cell types, notably glia, and rely on substances released by glia for their normal function. A deficit in glial response may disturb this critical neuronal-glial-neuronal interaction in Down syndrome (DS), leading to loss of neurons and other defects of development, and contribute to cognitive limitation and early onset of Alzheimer disease.

The hypothesis this paper will discuss is that normal neural development involves an activity-dependent release of substances from neurons, and that these substances act upon glia cells which in turn release substances that influence neurons to promote their survival and development. This glial influence affects cortical neurons and also the subcortical cholinergic neurons that project to the cerebral and hippocampal cortices to maintain cortical neuronal excitability and activity. The neuronal activity stimulates glial secretion of sustaining substances, in a reciprocally interactive cycle. Some aspect of this “virtuous cycle” is deficient in Down syndrome. The result is a small but slowly increasing deficit in activity-dependent support by glia cells which produces a gradually increasing abnormality of cortical and subcortical, perhaps especially cholinergic, function.


Nerve Growth Factor Down Syndrome Vasoactive Intestinal Peptide Basal Forebrain Ts65Dn Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag/Wien 2001

Authors and Affiliations

  • P. G. Nelson
    • 1
  • S. K. McCune
    • 2
  • A. M. Ades
    • 2
  • K. B. Nelson
    • 3
  1. 1.Laboratory of Developmental NeurobiologyNational Institute of Child Health and Human DevelopmentBethesdaUSA
  2. 2.Department of NeonatologyChildren’s National Medical CenterUSA
  3. 3.Neuroepidemiology BranchNational Institute of Neurological Disorders and StrokeBethesdaUSA

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