Functional and morphological alterations in compound transgenic mice overexpreszing Cu/Zn superoxide dismutaze and amyloid precursor protein

Catherine Harris-Cerruti, Ariel Kamsler, Batia Kaplan, Bruce Lamb, Menahem Segal, Yoram Groner

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Down's syndrome (DS), the phenotypic manifestation of trisomy 21, involves overexpression of chromosome 21-encoded genes. The gene for amyloid precursor protein (APP), known to be involved in AD pathology, resides on chromosome 21 along with the gene for Cu/Zn superoxide dismutase (SOD1), a key enzyme in the metabolism of oxygen free radicals. We investigated the consequences of a combined increase in APP and SOD1, in a double-transgenic (tg)-APP-SOD1 mouse. These mice expressed severe impairment in learning, working and long-term memory. Expression of long-term potentiation in hippocampal slices was impaired in both tg-SOD and tg-APP-SOD mice, but not in tg-APP mice, indicating that increased APP by itself did not affect in vitro synaptic plasticity. In tg-APP-SOD mice, membrane-bound high molecular weight APP species accumulated while APP cleavage products did not increase and levels of secreted APP were unchanged. Severe morphological damage, including lipofuscin accumulation and mitochondria abnormalities, were found in aged tg-APP-SOD but not in the other mice. Thus, a combined elevation of the two chromosome 21 genes in tg-APP-SOD mice induced age-dependent alterations in morphological and behavioural functions.

Original languageEnglish (US)
Pages (from-to)1174-1190
Number of pages17
JournalEuropean Journal of Neuroscience
Volume19
Issue number5
DOIs
StatePublished - Mar 2004
Externally publishedYes

Fingerprint

Amyloid beta-Protein Precursor
Superoxides
Transgenic Mice
Chromosomes, Human, Pair 21
Down Syndrome
Genes
Lipofuscin
Neuronal Plasticity
Long-Term Memory
Long-Term Potentiation
Free Radicals
Reactive Oxygen Species
Mitochondria
Molecular Weight
Learning
Pathology

Keywords

  • Cognitive behaviour
  • Down's syndrome
  • LTP
  • Mitochondria
  • Neuritic vacuolization
  • SOD1 APP

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Functional and morphological alterations in compound transgenic mice overexpreszing Cu/Zn superoxide dismutaze and amyloid precursor protein. / Harris-Cerruti, Catherine; Kamsler, Ariel; Kaplan, Batia; Lamb, Bruce; Segal, Menahem; Groner, Yoram.

In: European Journal of Neuroscience, Vol. 19, No. 5, 03.2004, p. 1174-1190.

Research output: Contribution to journalArticle

Harris-Cerruti, Catherine ; Kamsler, Ariel ; Kaplan, Batia ; Lamb, Bruce ; Segal, Menahem ; Groner, Yoram. / Functional and morphological alterations in compound transgenic mice overexpreszing Cu/Zn superoxide dismutaze and amyloid precursor protein. In: European Journal of Neuroscience. 2004 ; Vol. 19, No. 5. pp. 1174-1190.
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