Abstract

Hippocampal neurons from the fetal trisomy 16 mouse (Ts16), a model for Down syndrome, showed increased high-voltage- activated calcium currents in comparison to control diploid neurons. Ts16 neurons also bound more L-type calcium ligand. NMDA evoked currents in Ts16 neurons did not differ from currents in normal diploid neurons. Thus, this trisomy condition affects ionic responses that could have an impact on mental retardation in Down syndrome. We also investigated long-term potentiation (LTP), a model for learning and memory, in a new genetic model of Down syndrome, trisomy 16Dn mice, trisomic only for the part of mouse chromosome 16 that corresponds to human chromosome 21. The mice survive into adulthood. In hippocampal slices from trisomy 65Dn mice, LTP, induced by a single tetanizing pulse train at 100 Hz, was reduced, consistent with their learning impairment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000132-14
Application #
6097790
Study Section
Special Emphasis Panel (LN)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
National Institute on 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
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
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
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