Transgenic expression of human wild-type amyloid precursor protein decreases neurogenesis in the adult hippocampus

Nicole Naumann, A. Alpár, Uwe Ueberham, Thomas Arendt, Ulrich Gärtner

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Besides its role in Alzheimer's disease, the amyloid precursor protein (APP) is implicated in several physiological functions in neuronal tissue such as cell survival, neurite outgrowth, synaptic formation, and neuronal plasticity. The present study analyzed effects of human wild-type APP (hAPP) overexpression on adult hippocampal neurogenesis in transgenic mice. Mice were housed under either standard or enriched conditions, the latter to boost neurogenetic activity. Different aspects of neurogenesis including proliferation, survival, and differentiation were assessed by employing the BrdU-incorporation method and, in parallel, immunohistochemistry for the neuronal and glial markers NeuN and S100b, respectively. Overexpression of hAPP caused a significant decrease in cell proliferation under standard housing conditions. The relative increase in the proliferation rate following housing in enriched environment was not different to that observed in wild-type mice. Overexpression of hAPP, on the other hand, promoted the survival of newly generated cells, but just under conditions of standard housing. Findings further suggest that overexpression of hAPP suppresses the phenotypic shift toward neuronal differentiation under conditions of enriched environment. In summary, the results reveal a dual effect of APP on adult hippocampal neurogenesis, comprising antiproliferative and prosurvival activities.

Original languageEnglish
Pages (from-to)971-979
Number of pages9
JournalHippocampus
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Amyloid beta-Protein Precursor
Neurogenesis
Hippocampus
Neuronal Plasticity
Survival
Bromodeoxyuridine
Neuroglia
Transgenic Mice
Cell Survival
Alzheimer Disease
Immunohistochemistry
Cell Proliferation

Keywords

  • BrdU
  • Cell proliferation
  • Enriched environment
  • NeuN
  • S100b

ASJC Scopus subject areas

  • Cognitive Neuroscience

Cite this

Transgenic expression of human wild-type amyloid precursor protein decreases neurogenesis in the adult hippocampus. / Naumann, Nicole; Alpár, A.; Ueberham, Uwe; Arendt, Thomas; Gärtner, Ulrich.

In: Hippocampus, Vol. 20, No. 8, 08.2010, p. 971-979.

Research output: Contribution to journalArticle

Naumann, Nicole ; Alpár, A. ; Ueberham, Uwe ; Arendt, Thomas ; Gärtner, Ulrich. / Transgenic expression of human wild-type amyloid precursor protein decreases neurogenesis in the adult hippocampus. In: Hippocampus. 2010 ; Vol. 20, No. 8. pp. 971-979.
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