Abstract

Cultured neurons from Down syndrome (DS, trisomy 21, Ts21) fetuses and from fetuses of an animal model for DS, the trisomy 16 (Ts16) mouse, demonstrate many comparable abnormal electrical and biochemical properties. The hippocampus of another animal model, the Ts65Dn mouse, demonstrates abnormal long-term potentiation and depression, thus disturbed synaptic plasticity. Mental retardation in DS may be related to disturbed neuronal electrical properties and neuroplasticity. (1) The gene encoding the NR2A subunit of the NMDA receptor is on mouse chromosome 16, syntetic with human chromosome 21. Its expression is increased 2.5-fold in cultured Ts16 embryonic hippocampal neurons, but their NMDA-evoked currents are not altered. (2) Cultured tongue muscle cells from the Ts16 mouse model of DS have abnormal potassium and chloride membrane conductances. If present in DS muscle, such abnormalities may account for the hypotonia in this disorder. (3) Myoinositol, which is elevated in the DS brain, also is elevated in the brain of the Ts65Dn mouse model for DS. This model thus can be used to study the effect of such elevation on signal transduction and the phosphatidylinositol cycle.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000132-17
Application #
6521723
Study Section
(BPMS)
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Teipel, Stefan J; Alexander, Gene E; Schapiro, Marc B et al. (2004) Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. Brain 127:811-24
Teipel, Stefan J; Schapiro, Mark B; Alexander, Gene E et al. (2003) Relation of corpus callosum and hippocampal size to age in nondemented adults with Down's syndrome. Am J Psychiatry 160:1870-8
Cardenas, Ana Maria; Arriagada, Christian; Allen, David D et al. (2002) Cell lines derived from hippocampal neurons of the normal and trisomy 16 mouse fetus (a model for Down syndrome) exhibit neuronal markers, cholinergic function, and functional neurotransmitter receptors. Exp Neurol 177:159-70
Cardenas, Ana Maria; Allen, David D; Arriagada, Christian et al. (2002) Establishment and characterization of immortalized neuronal cell lines derived from the spinal cord of normal and trisomy 16 fetal mice, an animal model of Down syndrome. J Neurosci Res 68:46-58
Allen, David D; Cardenas, Ana Maria; Arriagada, Christian et al. (2002) A dorsal root ganglia cell line derived from trisomy 16 fetal mice, a model for Down syndrome. Neuroreport 13:491-6
Klein, R C; Siarey, R J; Caruso, A et al. (2001) Increased expression of NR2A subunit does not alter NMDA-evoked responses in cultured fetal trisomy 16 mouse hippocampal neurons. J Neurochem 76:1663-9
Galdzicki, Z; Siarey, R; Pearce, R et al. (2001) On the cause of mental retardation in Down syndrome: extrapolation from full and segmental trisomy 16 mouse models. Brain Res Brain Res Rev 35:115-45
Murphy, E J; Schapiro, M B; Rapoport, S I et al. (2000) Phospholipid composition and levels are altered in Down syndrome brain. Brain Res 867:18-Sep
Peng, S; Rapoport, S I; Pearce, R J et al. (2000) Abnormal chloride and potassium conductances in cultured embryonic tongue muscle from trisomy 16 mouse. Brain Res Dev Brain Res 122:193-7
Shetty, H U; Siarey, R J; Galdzicki, Z et al. (2000) Ts65Dn mouse, a Down syndrome model, exhibits elevated myo-inositol in selected brain regions and peripheral tissues. Neurochem Res 25:431-5

Showing the most recent 10 out of 12 publications