Abstract
Neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington’s (HD), Parkinson’s (PD) and Alzheimer’s diseases (AD), are characterized by the loss of structure and function of specific neuronal circuitry in the brain. As a result of this loss, behavioral symptoms occur progressively. Understanding the causes of neurodegeneration is fundamental for the development of new therapeutic targets. For this purpose, several animal models of neurodegenerative disorders have been generated and characterized. During the characterization, behavioral science plays a crucial role by identifying specific symptoms in these animal models of human disorders. Later on, it also allows scientists to verify the efficacy of new treatments. This chapter describes some of the standard tests used to assess behavioral symptoms present in mouse models of neurodegenerative disorders. A list of procedures is provided to evaluate motor skills for the study of ALS, HD, and PD models, and to evaluate spatial learning and memory for the study of AD models.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Wong, P. C., Cai, H., Borchelt, D. R., and Price, D. L. (2002) Genetically engineered mouse models of neurodegenerative diseases. Nat Neurosci. 5, 633–639.
Zoghbi, H. Y., and Botas, J. (2002) Mouse and fly models of neurodegeneration. Trends Genet. 18, 463–471.
Langui, D., Lachapelle, F., and Duyckaerts, C. (2007) [Animal models of neurodegenerative diseases]. Med Sci (Paris). 23, 180–186.
Jackson, M., Ganel, R., and Rothstein, J. D. (2002) Models of amyotrophic lateral sclerosis. Curr Protoc Neurosci. Chapter 9, Unit 9 13.
Ferrante, R. J. (2009) Mouse models of Huntington’s disease and methodological considerations for therapeutic trials. Biochim Biophys Acta. 1792, 506–520.
Heng, M. Y., Detloff, P. J., and Albin, R. L. (2008) Rodent genetic models of Huntington disease. Neurobiol Dis. 32, 1–9.
Chesselet, M. F., Fleming, S., Mortazavi, F., and Meurers, B. (2008) Strengths and limitations of genetic mouse models of Parkinson’s disease. Parkinsonism Relat Disord. 14 Suppl 2, S84–87.
Hattori, N., and Sato, S. (2007) Animal models of Parkinson’s disease: similarities and differences between the disease and models. Neuropathology. 27, 479–483.
Morrissette, D. A., Parachikova, A., Green, K. N., and LaFerla, F. M. (2009) Relevance of transgenic mouse models to human Alzheimer disease. J Biol Chem. 284, 6033–6037.
Gotz, J., and Ittner, L. M. (2008) Animal models of Alzheimer’s disease and frontotemporal dementia. Nat Rev Neurosci. 9, 532–544.
Crawley, J. N. (2008) Behavioral phenotyping strategies for mutant mice. Neuron. 57, 809–818.
Fleming, S. M. (2009) Behavioral outcome measures for the assessment of sensorimotor function in animal models of movement disorders. Int Rev Neurobiol. 89, 57–65.
Eriksen, J. L., and Janus, C. G. (2007) Plaques, tangles, and memory loss in mouse models of neurodegeneration. Behav Genet. 37, 79–100.
Steele, A. D., Jackson, W. S., King, O. D., and Lindquist, S. (2007) The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington’s and prion diseases. Proc Natl Acad Sci USA. 104, 1983–1988.
Yang, M., and Crawley, J. N. (2009) Simple behavioral assessment of mouse olfaction. Curr Protoc Neurosci. Chapter 8, Unit 8 24.
Pinto, L. H., and Enroth-Cugell, C. (2000) Tests of the mouse visual system. Mamm Genome. 11, 531–536.
Logue, S. F., Owen, E. H., Rasmussen, D. L., and Wehner, J. M. (1997) Assessment of locomotor activity, acoustic and tactile startle, and prepulse inhibition of startle in inbred mouse strains and F1 hybrids: implications of genetic background for single gene and quantitative trait loci analyses. Neuroscience. 80, 1075–1086.
Brooks, S. P., and Dunnett, S. B. (2009) Tests to assess motor phenotype in mice: a user’s guide. Nat Rev Neurosci. 10, 519–529.
Menalled, L., El-Khodor, B. F., Patry, M., Suarez-Farinas, M., Orenstein, S. J., Zahasky, B., Leahy, C., Wheeler, V., Yang, X. W., MacDonald, M., Morton, A. J., Bates, G., Leeds, J., Park, L., Howland, D., Signer, E., Tobin, A., and Brunner, D. (2009) Systematic behavioral evaluation of Huntington’s disease transgenic and knock-in mouse models. Neurobiol Dis. 35, 319–336.
Mura, A., Feldon, J., and Mintz, M. (1998) Reevaluation of the striatal role in the expression of turning behavior in the rat model of Parkinson’s disease. Brain Res. 808, 48–55.
Wooley, C. M., Sher, R. B., Kale, A., Frankel, W. N., Cox, G. A., and Seburn, K. L. (2005) Gait analysis detects early changes in transgenic SOD1(G93A) mice. Muscle Nerve. 32, 43–50.
Lalonde, R., Hayzoun, K., Selimi, F., Mariani, J., and Strazielle, C. (2003) Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor. Physiol Behav. 80, 333–339.
Barlow, C., Hirotsune, S., Paylor, R., Liyanage, M., Eckhaus, M., Collins, F., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D., and Wynshaw-Boris, A. (1996) Atm-deficient mice: a paradigm of ataxia telangiectasia. Cell. 86, 159–171.
Gallardo, G., Schluter, O. M., and Sudhof, T. C. (2008) A molecular pathway of neurodegeneration linking alpha-synuclein to ApoE and Abeta peptides. Nat Neurosci. 11, 301–308.
Kobayashi, D. T., and Chen, K. S. (2005) Behavioral phenotypes of amyloid-based genetically modified mouse models of Alzheimer’s disease. Genes Brain Behav. 4, 173–196.
Lalonde, R. (2002) The neurobiological basis of spontaneous alternation. Neurosci Biobehav Rev. 26, 91–104.
Morris, R. (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 11, 47–60.
Deacon, R. M., and Rawlins, J. N. (2006) T-maze alternation in the rodent. Nat Protoc. 1, 7–12.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Dumont, M. (2011). Behavioral Phenotyping of Mouse Models of Neurodegeneration. In: Manfredi, G., Kawamata, H. (eds) Neurodegeneration. Methods in Molecular Biology, vol 793. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-328-8_15
Download citation
DOI: https://doi.org/10.1007/978-1-61779-328-8_15
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-327-1
Online ISBN: 978-1-61779-328-8
eBook Packages: Springer Protocols