Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9 transgenic mice: Effect of long-term treatment with paroxetine

Louise Ørum Olesen, Mithula Sivasaravanaparan, Maurizio Severino, Alicia A. Babcock, Elena V. Bouzinova, Mark J. West, Ove Wiborg, Bente Finsen

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APPswe/PS1dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18 months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18 months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory.

Original languageEnglish
Pages (from-to)50-60
Number of pages11
JournalNeurobiology of Disease
Volume104
DOIs
StatePublished - 1 Aug 2017
Externally publishedYes

Keywords

  • APP/PS1 mice
  • Amyloid plaque load
  • Granule cells
  • Hippocampus
  • Neurogenesis
  • Paroxetine
  • SSRI
  • Spontaneous alternation behaviour

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