Skip to main content
SpringerLink
Log in

Chronobiometry of Behavioral Activity in the Ts65Dn Model of Down Syndrome

  • Original Paper
  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

Disruption of the sleep-wake cycle has been reported among individuals with Down syndrome (DS). Here we studied behavioral rhythms in adult male and female Ts65Dn mice, a model of DS. The overall behavioral activity of Ts65Dn and diploid (2N) littermates as defined by total movements (TM), movement time (MT), ambulatory movement time (AMT), time spent in center of arena (CT), jumps (JFP), rotational behavior (TURNS), and wheel-running activity (WRA) was recorded under a 12 h:12 h light–dark photocycle. During the light phase, Ts65Dn mice exhibited higher TM, MT, CT, JFP, and WRA compared to 2N littermates. During the dark phase, Ts65Dn and 2N mice differed only in CT and WRA, with the Ts65Dn group engaging in higher levels of both. There were no gender differences for any of the behavioral variables studied. Non-linear least-squares (Cosinor) analysis of the distribution of total behavioral activity (TM) indicated that Ts65Dn mice exhibited a slightly higher mean oscillation (i.e., mesor), but significantly lower amplitude in comparison to 2N mice, suggesting that levels of TM were elevated in trisomic mice but were relatively constant throughout the photocycle. The peak of the Ts65Dn TM rhythm was significantly phase-advanced, occurring approximately 4 h earlier than 2N mice. Overall, Ts65Dn mice were hyperactive and differed significantly in daily patterns of specific behaviors from those of 2N littermates. To control for the potential confound of retinal degeneration in Ts65Dn and 2N mice, we compared and found no difference between the TM rhythm parameters of 2N and non-retinally degenerate C57/129Sv mice, suggesting that abnormal behavioral rhythmicity in Ts65Dn mice may not due to the absence of rod and cone photoreceptors. These results serve as a starting point for further investigations into the physiological basis of sleep–wake disturbances in DS patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ambree O, Touma C, Gortz N, Keyvani K, Paulus W, Palme R, Sachser N (2006) Acitivty changes and marked stereotypic behavior precede Aβ pathology in TgCRND8 Alzheimer mice. Neurobiol. Aging 27:955–964

    Article  PubMed  CAS  Google Scholar 

  • Belichenko PV, Masliah E, Kleschevnikov AM, Villar AJ, Epstein CJ, Salehi A, Mobley WC (2004) Synaptic structural abnormalities in the Ts65Dn mouse model of Down Syndrome. J Comp Neurol 480:281–298

    Article  PubMed  Google Scholar 

  • Benavides-Piccione R, Ballesteros-Yanez I, de Lagran MM, Elston G, Estivill X, Fillat C, Defelipe J, Dierssen M (2004) On dendrites in Down syndrome and DS murine models: a spiny way to learn. Prog Neurobiol 74:111–126

    Article  PubMed  CAS  Google Scholar 

  • Bimonte-Nelson HA, Hunter CL, Nelson ME, Granholm AC (2003) Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome. Behav Brain Res 139:7–57

    Article  CAS  Google Scholar 

  • Chang B, Hawes NL, Hurd RE, Davisson, MT, Nusinowitz S, Heckenlively JR (2002) Retinal degeneration mutants in the mouse. Vision Res 42:517–525

    Article  PubMed  CAS  Google Scholar 

  • Cooper SA, Prasher VP (1998) Maladaptive behaviours and symptoms of dementia in adults with Down syndrome compared with adults with intellectual disability of other etiologies. J Intellect Disabil Res 42:293–300

    Article  PubMed  Google Scholar 

  • Cotton S, Richdale A (2006) Parental descriptions of sleep problems in children with autism, Down syndrome, and Prader–Willi syndrome. Res Dev Disabil 27:151–161

    Article  PubMed  Google Scholar 

  • Coussons-Read ME, Crnic LS (1996) Behavioral assessment of the Ts65Dn mouse, a model for Down syndrome: altered behavior in the elevated plus maze and open field. Behav Genet 26:7–13

    Article  PubMed  CAS  Google Scholar 

  • Costa AC, Walsh K, Davisson MT (1999) Motor dysfunction in a mouse model for Down syndrome. Physiol Behav 68:211–220

    Article  PubMed  CAS  Google Scholar 

  • Dahlqvist A, Rask E, Rosenqvist CJ, Sahlin C, Franklin KA (2003) Sleep apnea and Down syndrome. Acta Otolaryngol 123:1094–1097

    Article  PubMed  Google Scholar 

  • Davisson MT, Schmidt C, Akeson EC (1990) Segmental trisomy of murine chromosome 16: a new system for studying Down syndrome. In: Patteron D, Epstein CJ (eds) Molecular genetics of chromosome 21 and Down syndrome. Wiley-Liss, New York, pp. 263–280

    Google Scholar 

  • Demas GE, Nelson RJ, Krueger BK, Yarowsky PJ (1996) Spatial memory deficits in segmental trisomic Ts65Dn mice. Behav Brain Res 2:5–92

    Google Scholar 

  • Driscoll LL, Carroll JC, Moon J, Crnic LS, Levitsky DA, Strupp BJ (2004) Impaired sustained attention and error-induced stereotypy in the aged Ts65Dn mouse: a model of Down syndrome and Alzheimer’s disease. Behav Neurosci 118:1196–1205

    Article  PubMed  Google Scholar 

  • Easton A, Meerlo P, Bergmann B, Turek FW (2004) The suprachiasmatic nucleus regulates sleep timing and amount in mice. Sleep 27:1307–1318

    PubMed  Google Scholar 

  • Escorihuela RM, Fernandez-Teruel A, Vallina IF, Baamonde C, Lumbreras MA, Dierssen M, Tobena A, Florez J (1995) A behavioral assessment of Ts65Dn mice: a putative Down syndrome model. Neurosci Lett 199:43–146

    Article  Google Scholar 

  • Escorihuela RM, Vallina IF, Martinez-Cue C, Baamonde C, Dierssen M, Tobena A, Florez J, Fernandez-Teruel A (1998) Impaired short-and long-term memory in Ts65Dn mice, a model for Down syndrome. Neurosci Lett 247:171–174

    Article  PubMed  CAS  Google Scholar 

  • Ferguson SA, Kenneway DJ, Moyer RW (1999) Nicotine phase shifts the 6-sulphatoxymelatonin rhythm and induces c-Fos in the SCN of rats. Brain Res Bull 48:527–538

    Article  PubMed  CAS  Google Scholar 

  • Finkel SI (2003) Behavioral and psychological symptoms of dementia. Clin. Geriatr Med 19:799–824

    Article  PubMed  Google Scholar 

  • Hampton TG, Stasko MR, Kale A, Amende I, Costa AC (2004) Gait dynamics in trisomic mice: quantitative neurological traits of Down syndrome. Physiol Behav 82:381–389

    Article  PubMed  CAS  Google Scholar 

  • Hastings M, Maywood ES (2000) Circadian clocks in the mammalian brain. BioEssays 22:23–31

    Article  PubMed  CAS  Google Scholar 

  • Holtzman DM, Santucci D, Killbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, Johnson RM, Chen K, Sun Y, Carlson E, Alleva E, Epstein CJ, Mobley WC (1996) Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci USA 93:13333–13338

    Article  PubMed  CAS  Google Scholar 

  • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, A-beta elevation, and amyloid plaques in transgenic mice. Science 274:99–102

    Article  PubMed  CAS  Google Scholar 

  • Hunter CL, Isacson O, Nelson M, Bimonte-Nelson H, Seo H, Lin L, Ford K, Kindy MS, Granholm A-C (2003) Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down’s syndrome. Neurosci Res 45:437–445

    Article  PubMed  CAS  Google Scholar 

  • Klein SL, Kriegsfeld LJ, Hairston JE, Rau V, Nelson RJ, Yarowsky PJ (1996) Characterization of sensorimotor performance, reproductive and aggressive behaviors in segmental trisomic 16 (Ts65Dn) mice. Physiol Behav 60:1159–1164

    Article  PubMed  CAS  Google Scholar 

  • Krout KE, Kawano J, Mettenleiter TC, Loewy AD (2002) CNS inputs to the suprachiasmatic nucleus of the rat. Neuroscience 110:73–92

    Article  PubMed  CAS  Google Scholar 

  • Lalonde R, Dumont M, Staufenbiel M, Sturchler-Pierrat C, Strazielle C (2002) Spatial learning, exploration, anxiety, motor coordination in female APP23 transgenic mice with the Swedish mutation. Brain Res 956:36–44

    Article  PubMed  CAS  Google Scholar 

  • Levanon A, Tarasiuk A, Tal A (1999) Sleep characteristics in children with Down syndrome. J Pediatr 134:755–760

    Article  PubMed  CAS  Google Scholar 

  • Low-Zeddies SS, Takahashi JS (2001) Chimera analysis of the Clock mutation in mice shows that complex cellular integration determines circadian behavior. Cell 105:25–42

    Article  PubMed  CAS  Google Scholar 

  • Liu DP, Schnidt C, Billings T, Davisson MT (2003) Quantitative PCR genotyping assay for the Ts65Dn mouse model of Down syndrome. Biotechniques 35:1–7

    Google Scholar 

  • Marashi V, Barnekow A, Ossendorf E, Sachser N (2003) Effects of different forms of environmental enrichment on behavioral, endocrinological, and immunological parameters in male mice. Horm Behav 43:281–292

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Cue C, Baamonde C, Lumbreras M, Paz J, Davisson MT, Schmidt C, Diersson M, Florez J (2002) Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome. Behav Brain Res 134:185–200

    Article  PubMed  Google Scholar 

  • Moore RY (1996) Entrainment pathways and the functional organization of the circadian system. Prog Brain Res 111:103–119

    Article  PubMed  CAS  Google Scholar 

  • Mrak RE, Griffin WS (2004) Trisomy 21 and the brain. J Neuropathol Exp Neurol 63:679–85

    PubMed  CAS  Google Scholar 

  • Mrosovsky N (2003) Contribution of classic photoreceptors to entrainment. J Comp Physiol A 189:69–73

    CAS  Google Scholar 

  • Mrosovsky N (2003) Aschoff’s rule in retinally degenerate mice. J Comp Physiol A 189:75–78

    CAS  Google Scholar 

  • Niedermayer E (2001) Frontal lobe disinhibition, Rett syndrome and attention deficit hyperactivity disorder. Clin Electroencephalogr 32:20–23

    Google Scholar 

  • Nelson DL, Gibbs RA (2004) The critical region in Trisomy 21. Science 306:619–621

    Article  PubMed  CAS  Google Scholar 

  • Pitovcakova J, Makatsori A, Sulcova A, Jezova D (2005) Felbamate reduces hormone release and locomotor hypoactivity induced by repeated stress of social defeat in mice. Eur Neuropsychopharmacol 15:153–158

    Article  CAS  Google Scholar 

  • Provencio I, Wong S, Lederman AB, Argamaso SM, Foster RG (1994) Visual and circadian responses to light in aged retinally degenerate mice. Vision Res 34:1799–1806

    Article  PubMed  CAS  Google Scholar 

  • Provencio I, Cooper HM, Foster RG (1998) Retinal projections in mice with inherited retinal degeneration: implications for circadian photoentrainment. J Comp Neurol 395:417–439

    Article  PubMed  CAS  Google Scholar 

  • Ralph MR, Foster RG, Davis FC, Menaker M (1990) Transplanted suprachiasmatic nucleus determines circadian period. Science 247:975–978

    Article  PubMed  CAS  Google Scholar 

  • Richtsmeier JT, Zumwalt A, Carlson EJ, Epstein CJ, Reeves RH (2002) Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome. Am J Med Genet 107:317–324

    Article  PubMed  Google Scholar 

  • Sancar A (2000) Cryptochrome: the second photoactive pigment in the eye and its role in circadian photoreception. Annu Rev Biochem 69:31–67

    Article  PubMed  CAS  Google Scholar 

  • Selby CP, Thompson C, Schmitz TM, van Gelder RN, Sancar A (2000) Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc Natl Acad Sci USA 97:14697–14702

    Article  PubMed  CAS  Google Scholar 

  • Seo H, Isacson O (2005) Abnormal APP, cholinergic and cognitive function in Ts65Dn Down’s model mice. Exp Neurol 193:469–480

    Article  PubMed  CAS  Google Scholar 

  • Stewart LS, Potok A, Camper SA, Stifani S (2005) Runx1 expression defines a subpopulation of displaced amacrine cells in the developing mouse retina. J Neurochem 94:1739–1745

    Article  PubMed  CAS  Google Scholar 

  • Tate B, Aboody-Guterman KS, Morris AM, Walcott EC, Majocha RE, Marotta CA (1992) Disruption of circadian regulation by brain grafts that overexpress Alzheimer beta/A4 amyloid. Proc Natl Acad Sci USA 89:7090–7094

    Article  PubMed  CAS  Google Scholar 

  • Teipel SJ, Hampel H (2006) Neuroanatomy of Down syndrome in vivo: a model of preclinical Alzheimer’s disease. Behav Genet 36:405–415

    Article  PubMed  Google Scholar 

  • Teicher MH, Barber NI (1990) COSIFIT: an interactive program for simultaneous multioscillator Cosinor analysis of time-series data. Comp Biomed Res 23:283–295

    Article  CAS  Google Scholar 

  • Tsiouris JA, Brown WT (2004) Neuropyschiatric symptoms of fragile X syndrome: pathophysiology and pharmacotherapy. CNS Drugs 18:687–703

    Article  PubMed  CAS  Google Scholar 

  • Turek FW (1985) Circadian neural rhythms in mammals. Ann Rev Physiol 47:49–64

    Article  CAS  Google Scholar 

  • Turner CA, Presti MF, Newman HA, Bugenhagen P, Crnic L, Lewis MH (2001) Spontaneous stereotypy in an animal model of Down syndrome: Ts65Dn mice. Behav Genet 31:393–400

    Article  PubMed  CAS  Google Scholar 

  • Vicari S (2006) Motor development and neuropsychological patterns in persons with Down syndrome. Behav Genet 36:355–364

    Article  PubMed  Google Scholar 

  • Vitiello MV, Prinz PN (1989) Alzheimer’s disease. Sleep and sleep/wake patterns. Clin Geriatr Med 5:289–299

    PubMed  CAS  Google Scholar 

  • Wilsor JP, Edgar DM, Yesavage J, Ryan HS, McCormick CM, Lapustea N, Murphy GM (2005) Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer’s disease: a role for cholinergic transmission. Neuroscience 131:375–385

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Zhengpheng Jia, Zarko Todorovski, Ilyas Aleem, and the Laboratory Animal Services at the Hospital for Sick Children for assistance. We also thank Dr. Lily Shen for the breeding and genotyping of the Ts65Dn mouse line. This work was supported by grants from The Hospital for Sick Children Down Syndrome Fund (#3217656151) to M.A.C. and The Canadian Institutes of Health Research (#3210016078) to O.C.S., III. L.S.S. is the recipient of a postdoctoral fellowship (#PDF-313950-2005) from the Natural Sciences and Engineering Research Council of Canada.

Author information

Authors and Affiliations

  1. Brain and Behavior Research Program, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8

    Lee S. Stewart, Miguel A. Cortez & O. Carter Snead III

  2. Division of Neurology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8

    Miguel A. Cortez & O. Carter Snead III

  3. Department of Pediatrics, Faculty of Medicine, The University of Toronto, 555 University Avenue, Toronto, ON, Canada, M5G 1X8

    Miguel A. Cortez & O. Carter Snead III

  4. Department of Psychology, Laurentian University, Sudbury, ON, Canada, P3E 2C6

    Michael A. Persinger

Authors
  1. Lee S. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael A. Persinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel A. Cortez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. Carter Snead III
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. Carter Snead III.

Additional information

Edited by Pierre Roubertoux

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stewart, L.S., Persinger, M.A., Cortez, M.A. et al. Chronobiometry of Behavioral Activity in the Ts65Dn Model of Down Syndrome. Behav Genet 37, 388–398 (2007). https://doi.org/10.1007/s10519-006-9119-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-006-9119-y

Keywords

Search

Navigation