Reduction in open field activity in the absence of memory deficits in the AppNL-G-F knock-in mouse model of Alzheimer's disease

Behav Brain Res. 2018 Jan 15:336:177-181. doi: 10.1016/j.bbr.2017.09.006. Epub 2017 Sep 5.

Abstract

The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the AppNL-F and AppNL-G-F mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of AppNL-G-F/NL-G-F (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between AppNL-G-F/NL-G-F and wild-type mice. Further assessment of these mice using the novel object recognition test and Morris water maze also revealed no differences between AppNL-G-F/NL-G-F and wild-type mice. Despite a lack of demonstrated cognitive deficits, we report a reduction in locomotor/exploratory activity in an open field. Histological examination of AppNL-G-F/NL-G-F mice showed widespread distribution of amyloid plaques at this age. We conclude that whilst at six-months of age, memory deficits are not sufficiently robust to be replicated in varying environments, amyloid plaque burden is significant in AppNL-G-F/NL-G-F knock-in brain.

Keywords: Alzheimer’s disease; App(NL-G-F); Morris water maze; Y-maze; novel object recognition test; open field.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Behavior, Animal / physiology
  • Brain / metabolism
  • Cognitive Dysfunction / pathology
  • Disease Models, Animal
  • Exploratory Behavior / physiology
  • Gene Knock-In Techniques
  • Male
  • Maze Learning
  • Memory Disorders / genetics
  • Memory, Short-Term / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Plaque, Amyloid / genetics*
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor