[en] Despite its wide application in studies on memory and disease-related cognitive impairment, the use of the novel object recognition (NOR) test in research on aging has been limited and produced conflicting results. The purpose of this study was to characterize NOR across the lifespan of male C57BL/6 mice (3, 6, 9, 12, 15, and 24 months), the most popular rodent model of aging. NOR, measured after a delay of 24 hours, was analyzed with respect to variability, its dependence on locomotor and exploratory activity, and with an emphasis on its temporal dynamics. The latter has been recognized in rats, but never been investigated in mice. We find that although locomotor activity decreases monotonically above 3 months of age, exploratory activity in our setup remains constant and sufficient for NOR testing up to 12 months. As a major finding, we show that NOR depends on exploration time in the test phase in an age-dependent manner. Whereas NOR in our paradigm remains significant up to at least 20 seconds total exploration time in 3 and 6 months old mice, novel object preference at 9 and 12 months of age is detectable after 10 seconds exploration, but decreases rapidly and is missed when the first 20 seconds are analyzed. Analysis of the first 2 minutes of the test phase does not detect NOR except for 3 months old mice. We conclude that temporal aspects of NOR have been neglected and must be considered when making comparisons between or within mice at different ages.
Disciplines :
Neurologie
Auteur, co-auteur :
Traschütz, Andreas; Department of Neurology University Hospital of Bonn, Germany. Electronic address: andreas.traschuetz@ukb.uni-bonn.de
Kummer, Markus P; Department of Neurodegenerative Diseases and Gerontopsychiatry/Neurology, University Hospital of Bonn, Germany. Electronic address: mpkummer@uni-bonn.de
Schwartz, Stephanie; Department of Neurodegenerative Diseases and Gerontopsychiatry/Neurology, University Hospital of Bonn, Germany. Electronic address: stephanie.schwartz@ukb.uni-bonn.de
HENEKA, Michael ; Department of Neurodegenerative Diseases and Gerontopsychiatry/Neurology, University Hospital of Bonn, Germany, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Electronic address: michael.heneka@ukb.uni-bonn.de
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Variability and temporal dynamics of novel object recognition in aging male C57BL/6 mice.
Else Kröner-Fresenius Foundation via the Else Kröner-Forschungskolleg Bonn
Subventionnement (détails) :
This work was supported by the Else Kröner-Fresenius Foundation via the Else Kröner-Forschungskolleg Bonn .This work was supported by the Else Kr?ner-Fresenius Foundation via the Else Kr?ner-Forschungskolleg Bonn.
Dean, R.L. 3rd, Scozzafava, J., Goas, J.A., Regan, B., Beer, B., Bartus, R.T., Age-related differences in behavior across the life span of the C57BL/6J mouse. Exp. Aging Res. 7 (1981), 427–451.
Dellu, F., Piazza, P.V., Mayo, W., Le Moal, M., Simon, H., Novelty-seeking in rats–biobehavioral characteristics and possible relationship with the sensation-seeking trait in man. Neuropsychobiology 34 (1996), 136–145.
Dere, E., Huston, J.P., De Souza Silva, M.A., The pharmacology, neuroanatomy and neurogenetics of one-trial object recognition in rodents. Neurosci. Biobehav. Rev. 31 (2007), 673–704.
Dix, S.L., Aggleton, J.P., Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition. Behav. Brain Res. 99 (1999), 191–200.
Ennaceur, A., Delacour, J., A new one-trial test for neurobiological studies of memory in rats: 1: Behavioral data. Behav. Brain Res. 31 (1988), 47–59.
Ennaceur, A., Michalikova, S., Bradford, A., Ahmed, S., Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks. Behav. Brain Res. 159 (2005), 247–266.
Ennaceur, A., One-trial object recognition in rats and mice: methodological and theoretical issues. Behav. Brain Res. 215 (2010), 244–254.
Fahlstrom, A., Yu, Q., Ulfhake, B., Behavioral changes in aging female C57BL/6 mice. Neurobiol. Aging 32 (2011), 1868–1880.
Frick, K.M., Gresack, J.E., Sex differences in the behavioral response to spatial and object novelty in adult C57BL/6 mice. Behav. Neurosci. 117 (2003), 1283–1291.
Frick, K.M., Burlingame, L.A., Arters, J.A., Berger-Sweeney, J., Reference memory, anxiety and estrous cyclicity in C57BL/6NIA mice are affected by age and sex. Neuroscience 95 (2000), 293–307.
Grayson, B., Leger, M., Piercy, C., Adamson, L., Harte, M., Neill, J.C., Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents. Behav. Brain Res. 285 (2015), 176–193.
Heneka, M.T., Kummer, M.P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493 (2013), 674–678.
Ingram, D.K., Archer, J.R., Harrison, D.E., Reynolds, M.A., Physiological and behavioral correlates of lifespan in aged C57BL/6J mice. Exp. Gerontol. 17 (1982), 295–303.
Ingram, D.K., Motor performance variability during aging in rodents: assessment of reliability and validity of individual differences. Ann. N. Y. Acad. Sci. 515 (1988), 70–96.
Kilkenny, C., Browne, W., Cuthill, I.C., Emerson, M., Altman, D.G., Group, N.C.R.R.G.W., Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br. J. Pharmacol. 160 (2010), 1577–1579.
Leger, M., Quiedeville, A., Bouet, V., Haelewyn, B., Boulouard, M., Schumann-Bard, P., et al. Object recognition test in mice. Nat. Protoc. 8 (2013), 2531–2537.
Messier, C., Object recognition in mice: improvement of memory by glucose. Neurobiol. Learn Mem. 67 (1997), 172–175.
Mumby, D.G., Pinel, J.P., Rhinal cortex lesions and object recognition in rats. Behav. Neurosci. 108 (1994), 11–18.
Sik, A., van Nieuwehuyzen, P., Prickaerts, J., Blokland, A., Performance of different mouse strains in an object recognition task. Behav. Brain Res. 147 (2003), 49–54.
Stansfield, K.H., Kirstein, C.L., Effects of novelty on behavior in the adolescent and adult rat. Dev. Psychobiol. 48 (2006), 10–15.
von Bohlen und Halbach, O., Zacher, C., Gass, P., Unsicker, K., Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice. J. Neurosci. Res. 83 (2006), 525–531.
