Understanding mental retardation in down's syndrome using trisomy 16 mouse models

  • Galdzicki Z
  • Siarey R
  • 37

    Readers

    Mendeley users who have this article in their library.
  • 65

    Citations

    Citations of this article.

Abstract

Mental retardation in Down's syndrome, human trisomy 21, is characterized by developmental delays, language and memory deficits and other cognitive abnormalities. Neurophysiological and functional information is needed to understand the mechanisms of mental retardation in Down's syndrome. The trisomy mouse models provide windows into the molecular and developmental effects associated with abnormal chromosome numbers. The distal segment of mouse chromosome 16 is homologous to nearly the entire long arm of human chromosome 21. Therefore, mice with full or segmental trisomy 16 (Ts65Dn) are considered reliable animal models of Down's syndrome. Ts65Dn mice demonstrate impaired learning in spatial tests and abnormalities in hippocampal synaptic plasticity. We hypothesize that the physiological impairments in the Ts65Dn mouse hippocampus can model the suboptimal brain function occuring at various levels of Down's syndrome brain hierarchy, starting at a single neuron, and then affecting simple and complex neuronal networks. Once these elements create the gross brain structure, their dysfunctional activity cannot be overcome by extensive plasticity and redundancy, and therefore, at the end of the maturation period the mind inside this brain remains deficient and delayed in its capabilities. The complicated interactions that govern this aberrant developmental process cannot be rescued through existing compensatory mechanisms. In summary, overexpression of genes from chromosome 21 shifts biological homeostasis in the Down's syndrome brain to a new less functional state.

Author-supplied keywords

  • Down's syndrome
  • Mental retardation
  • Mouse
  • Neurodevelopment
  • Synaptic plasticity
  • Trisomy 16
  • Trisomy 21
  • Ts1Cje
  • Ts65Dn

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Z. Galdzicki

  • R. J. Siarey

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free