Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APP(swe)/PS1(dE9) transgenic mice: Effect of long-term treatment with paroxetine

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

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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 APP(swe)/PS1(dE9) 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. (C) 2017 Elsevier Inc. All rights reserved.

Original languageEnglish
JournalNeurobiology of Disease
Volume104
Pages (from-to)50-60
Number of pages11
ISSN0969-9961
DOIs
Publication statusPublished - Aug 2017

Keywords

  • Aging/genetics
  • Alzheimer Disease/drug therapy
  • Amyloid beta-Peptides/metabolism
  • Amyloid beta-Protein Precursor/genetics
  • Animals
  • Bromodeoxyuridine/metabolism
  • Cytochrome P-450 CYP2D6 Inhibitors/therapeutic use
  • Dentate Gyrus/drug effects
  • Disease Models, Animal
  • Exploratory Behavior/drug effects
  • Maze Learning/drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins/metabolism
  • Mutation/genetics
  • Neural Stem Cells/drug effects
  • Neurogenesis/drug effects
  • Neurons/drug effects
  • Neuropeptides/metabolism
  • Paroxetine/therapeutic use
  • Presenilin-1/genetics

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