Elsevier

Neuroscience

Volume 148, Issue 4, 21 September 2007, Pages 825-832
Neuroscience

Behavioural neuroscience
Quantitative measurement of postural sway in mouse models of human neurodegenerative disease

https://doi.org/10.1016/j.neuroscience.2007.07.025Get rights and content

Abstract

Detection of motor dysfunction in genetic mouse models of neurodegenerative disease requires reproducible, standardized and sensitive behavioral assays. We have utilized a center of pressure (CoP) assay in mice to quantify postural sway produced by genetic mutations that affect motor control centers of the brain. As a positive control for postural instability, wild type mice were injected with harmaline, a tremorigenic agent, and the average areas of the 95% confidence ellipse, which measures 95% of the CoP trajectory values recorded in a single trial, were measured. Ellipse area significantly increased in mice treated with increasing doses of harmaline and returned to control values after recovery. We also examined postural sway in mice expressing mutations that mimic frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (T-279, P301L or P301L–nitric oxide synthase 2 (NOS2)−/− mice) and that demonstrate motor symptoms. These mice were then compared with a mouse model of Alzheimer’s disease (APPSwDI mice) that demonstrates cognitive, but not motor deficits. T-279 and P301L-NOS2−/− mice demonstrated a significant increase in CoP ellipse area compared with appropriate wild type control mice or to mice expressing the P301L mutation alone. In contrast, postural instability was significantly reduced in APPSwDI mice that have cognitive deficits but do not have associated motor deficits. The CoP assay provides a simple, sensitive and quantitative tool to detect motor deficits resulting from postural abnormalities in mice and may be useful in understanding the underlying mechanisms of disease.

Section snippets

Animals

Transgenic mice (APPSwDI) containing the Swedish, Dutch (E22Q) and Iowa (D23N) amyloid precursor protein (APP) mutations, were generated as described (Davis et al., 2004) and were a generous gift from Dr. William Van Nostrand, Stony Brook University, Stony Brook, NY, USA. P301L mice expressing the P301L human tau mutation were generated as described by Lewis et al. (2000) and were a generous gift from Drs. Lewis and Hutton, Mayo Clinic at Jacksonville, Jacksonville, FL, USA. Bigenic mice were

Results

To verify that body sway could be detected in mice using CoP analysis, we injected young adult (18–25 weeks old), wild type mice with varying doses of harmaline, a known tremorigenic agent. Two concentrations of harmaline were studied using two separate groups of mice (5 mg/kg and 10 mg/kg with five mice per dose) and CoP was performed before treatment, approximately 5 min after induction of tremors and approximately 24 h post-treatment. As shown in Fig. 3, action tremors generated by harmaline

Discussion

Our data demonstrate that CoP analysis provides a simple and quantitative tool to examine motor deficits in pharmacological or genetic mouse models of neurodegenerative diseases. CoP analysis measures postural stability during quiet stance and provides an integrated measure of muscle activity in the inactive (stationary) rodent. Abnormal postural sway in rodents resting on four limbs is likely to represent a mixture of motor deficits; including tremor, imbalance and bradykinesia that each can

Acknowledgments

The authors would like to thank AMTI for their cooperative efforts in designing a suitable mouse CoP platform and for providing the necessary software for analysis.

References (32)

  • A. Zumwalt et al.

    A force platform for measuring ground reaction forces in small animal locomotion

    J Biomech

    (2006)
  • R. Bhidayasiri

    Differential diagnosis of common tremor syndromes

    Postgrad Med J

    (2005)
  • M. Bove et al.

    Posturographic analysis of balance control in patients with essential tremor

    Mov Disord

    (2006)
  • H. Braak et al.

    Stages in the development of Parkinson’s disease related pathology

    Cell Tissue Res

    (2004)
  • M.A. Cenci et al.

    Animal models of neurological deficits: how relevant is the rat?

    Nat Rev

    (2002)
  • C. Colton et al.

    NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer’s disease

    Proc Natl Acad Sci U S A

    (2006)
  • Cited by (14)

    • Objective detection of microtremors in netrin-G2 knockout mice

      2021, Journal of Neuroscience Methods
      Citation Excerpt :

      Quantitative methods of tremor detection for rodent models have been developed since the 1950s based on various tools including: wire coils and magnets (Dill et al., 1968; Moore et al., 1957; Shinozaki, 1984), gramophone or phono cartridge pick-ups (Agarwal and Bose, 1967; Ahmed and Taylor, 1959; Kelly and Naylor, 1974), strain gauges (Bekar et al., 2008; Fowler et al., 2001; Gerhart et al., 1982; Johnson et al., 1986; Martin et al., 2005; Yen and Day, 1965), and electromyography (Bekar et al., 2008; Günther et al., 1983; Hosoi et al., 2019; Milner et al., 1995; Sinton et al., 1989; Yamazaki et al., 1979). Other methods include piezo devices (Da Fonseca et al., 2001; Otis et al., 1969; Paterson et al., 2009; White et al., 2016), speakers (Gothóni et al., 1981; Kralic et al., 2005; Remington and Anisman, 1976), accelerometers (Hallberg et al., 1985; Kistler et al., 2002; Milner et al., 1995; Park et al., 2010; Sinton et al., 1989), ultrasonic transducers (Young et al., 1996, 2000), a Hall effect sensor (Hutchinson et al., 2007), an optical sensor (Cavallo et al., 2008), video cameras (Baker et al., 2000; Finn et al., 1997), and a smartphone (Carlsen et al., 2019). Some of them have been commercialized (Fowler et al., 2001; Hutchinson et al., 2007; Martin et al., 2005); however, there is no standard method.

    • Dynamic footprint based locomotion sway assessment in α-synucleinopathic mice using Fast Fourier Transform and Low Pass Filter

      2018, Journal of Neuroscience Methods
      Citation Excerpt :

      For translational studies of disorders, it is important to use sensitive assays for the quantitative evaluation of symptoms in animal models and for comparing such measures with the clinical correlates. With the aim of quantitatively describe progression of disorders in rodent models, behavioral tests are commonly used, including open field locomotion test, runway locomotion test, cylinder test, running wheel, rotometer, rotarod, raised beam test, footprint analysis, swimming test, staircase reaching test, acoustic startle chamber (Brooks and Dunnett, 2009), treadmill walking test (Wooley et al., 2009) and CoP assay (Hutchinson et al., 2007). Along with this line, an automated runway locomotion analysis for rodents named “CatWalk” was developed by Hamers and colleagues (Hamers et al., 2006, 2001).

    • Löfgren syndrome as an acute presentation of sarcoidoisis

      2018, Revista Colombiana de Reumatologia
    View all citing articles on Scopus
    View full text