Hyperactive behaviour in the mouse model of mucopolysaccharidosis IIIB in the open field and home cage environments

A Langford-Smith1, M Malinowska, K J Langford-Smith

  • 1Stem Cell & Neurotherapies, School of Biomedicine, University of Manchester, UK.

Insights

Behavioral testing in Mucopolysaccharidosis IIIB (MPS IIIB) mouse models reveals hyperactivity. The open field test, conducted shortly after lights on, effectively identifies neurobehavioral changes crucial for evaluating new therapies.

Area of Science:

  • Neuroscience
  • Genetics
  • Animal Models

Background:

  • Mucopolysaccharidosis IIIB (MPS IIIB) is a neurodegenerative lysosomal storage disorder with no current effective treatment.
  • Behavioral testing in MPS IIIB mouse models is vital for assessing neurodegeneration and therapeutic efficacy, but existing data are inconsistent.
  • Discrepancies in behavioral data may stem from variations in open field habituation and home cage testing protocols.

Purpose of the Study:

  • To investigate the impact of open field habituation and home cage behavior on the reliability of behavioral assessments in MPS IIIB mice.
  • To determine optimal conditions for behavioral testing in MPS IIIB mouse models to ensure consistent and interpretable results.

Main Methods:

  • Eight-month-old wild-type and MPS IIIB mice underwent a 1-hour open field test 1.5 hours after lights on.
  • A 24-hour home cage behavior test was conducted after 24 hours of acclimatization for both groups.
  • Behavioral parameters including hyperactivity, exploratory behavior, immobility, and anxiety were analyzed.

Main Results:

  • MPS IIIB mice exhibited hyperactivity with increased exploratory behavior and reduced immobility in the 1-hour open field test.
  • No significant differences in anxiety levels were observed between MPS IIIB and wild-type mice.
  • The 24-hour home cage test yielded less reliable results, showing increased hyperactivity but also increased immobility in MPS IIIB mice.
  • Behavioral differences in MPS IIIB mice were most pronounced at 1 hour into the open field test, coinciding with their peak activity.

Conclusions:

  • The open field test, particularly when performed within 1-2 hours after lights on, is a reliable method for detecting hyperactivity in MPS IIIB mice.
  • This standardized behavioral assay is a valuable tool for evaluating the efficacy of novel therapies targeting neurodegeneration in MPS IIIB.
  • Optimizing testing timing is critical for maximizing the success and consistency of behavioral assessments in MPS IIIB mouse models.

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