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Spatial Disorientation Under Dark Conditions Across Development in an Alzheimer's Disease Mouse Model.

Ashley A Blackwell1, Francine M Jodelka2, Rami I Lake1

  • 1Northern Illinois University, Department of Psychology, DeKalb, IL 60115, United States.

Neuroscience
|January 1, 2023
PubMed
Summary

Alzheimer's disease (AD) mouse models show spatial disorientation, a key wandering behavior, by two months of age. This impairment is worse in darkness, highlighting a new tool for testing AD therapeutics.

Keywords:
Alzheimer’s diseaseTgCRND8 miceacetylcholinesterasedark open fieldself-movement cuesspatial disorientation

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Area of Science:

  • Neuroscience
  • Behavioral Science
  • Genetics

Background:

  • Alzheimer's disease (AD) is linked to brain changes and cognitive issues like wandering.
  • Wandering behavior can be severe and appear early in individuals with specific genetic mutations.
  • Genetic mouse models are crucial for studying AD progression and testing treatments.

Purpose of the Study:

  • To assess spatial disorientation in CRND8 AD mouse models at prodromal stages.
  • To investigate the role of different sensory cues in maintaining spatial orientation in AD mice.
  • To establish the dark open field test as a tool for evaluating AD-related spatial disorientation.

Main Methods:

  • Utilized female transgenic CRND8 AD mice and control littermates at two and four months of age.
  • Employed a sequential open field behavior test under varying light conditions (dark vs. visual cues).
  • Analyzed the ability of mice to maintain spatial orientation using self-movement and environmental cues.

Main Results:

  • Spatial disorientation was evident at two months and worsened by four months in AD mice, particularly in darkness.
  • AD mice showed preserved spatial orientation when visual environmental cues were available.
  • Impaired processing of self-movement cues was documented in the AD mouse model.

Conclusions:

  • The dark open field test effectively captures spatial disorientation in AD mouse models.
  • This behavioral paradigm can serve as a valuable tool for assessing novel therapeutic interventions for AD.
  • Findings suggest early-onset navigation deficits in AD, impacting therapeutic development strategies.