Neurobiology of Aging
Volume 31, Issue 4 , Pages 625-635 , April 2010

Dogs with canine counterpart of Alzheimer's disease lose noradrenergic neurons

  • Daniel Insua

      Affiliations

    • Departamento de Ciencias Clínicas Veterinarias, Facultad de Veterinaria de Lugo, Universidad de Santiago de Compostela, 27002 Lugo, Spain
    • ,
  • María-Luisa Suárez

      Affiliations

    • Departamento de Ciencias Clínicas Veterinarias, Facultad de Veterinaria de Lugo, Universidad de Santiago de Compostela, 27002 Lugo, Spain
    • ,
  • Germán Santamarina

      Affiliations

    • Departamento de Ciencias Clínicas Veterinarias, Facultad de Veterinaria de Lugo, Universidad de Santiago de Compostela, 27002 Lugo, Spain
    • ,
  • Manuel Sarasa

      Affiliations

    • Araclon Biotech, Paseo Independencia N° 30 2A, 50004 Zaragoza, Spain
    • ,
  • Pedro Pesini

      Affiliations

    • Araclon Biotech, Paseo Independencia N° 30 2A, 50004 Zaragoza, Spain
    • Corresponding Author InformationCorresponding author. Tel.: +34 976 796 562; fax: +34 976 217 802.

Received 6 December 2007 ,Revised 25 March 2008 ,Accepted 18 May 2008.

References 

  1. Adams B, Chan A, Callahan H, Siwak C, Tapp D, Ikeda-Douglas C, et al. Use of a delayed non-matching to position task to model age-dependent cognitive decline in the dog. Behav. Brain Res. 2000;108(1):47–56
  2. Aston-Jones G, Shipley MT, Grzanna R. The locus coeruleus, A5 and A7 noradrenergic cell groups. In:  Paxinos G editors. The Rat Nervous System. 2nd Ed.. San Diego: Academic Press; 1995;p. 183–213
  3. Berridge CW, Waterhouse BD. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes.. Brain Res. Brain Res. Rev. 2003;42(1):33–84
  4. Bondareff W, Mountjoy CQ, Roth M. Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Neurology. 1982;32(2):164–168
  5. Burke WJ, Li SW, Schmitt CA, Xia P, Chung HD, Gillespie KN. Accumulation of 3,4-dihydroxyphenylglycolaldehyde, the neurotoxic monoamine oxidase A metabolite of norepinephrine, in locus ceruleus cell bodies in Alzheimer's disease: mechanism of neuron death. Brain Res. 1999;816(2):633–637
  6. Busch C, Bohl J, Ohm TG. Spatial, temporal and numeric analysis of Alzheimer changes in the nucleus coeruleus. Neurobiol. Aging. 1997;18(4):401–406
  7. Chan-Palay V, Asan E. Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. J. Comp. Neurol. 1989;287(3):373–392
  8. Chan-Palay V, Asan E. Quantitation of catecholamine neurons in the locus coeruleus in human brains of normal young and older adults and in depression. J. Comp. Neurol. 1989;287(3):357–372
  9. Coggeshall RE, La Forte R, Klein CM. Calibration of methods for determining numbers of dorsal root ganglion cells. J. Neurosci. Methods. 1990;35(3):187–194
  10. Colle M-A, Hauw J-J, Crespeau F, Uchihara T, Akiyama H, Checler F, et al. Vascular and parenchymal Abeta deposition in the aging dog: correlation with behavior. Neurobiol. Aging. 2000;21(5):695–704
  11. Cummings BJ, Head E, Afagh AJ, Milgram NW, Cotman CW. Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine. Neurobiol. Learn. Mem. 1996;66(1):11–23
  12. Cummings BJ, Head E, Ruehl W, Milgram NW, Cotman CW. The canine as an animal model of human aging and dementia. Neurobiol. Aging. 1996;17(2):259–268
  13. Dringenberg HC. Alzheimer's disease: more than a ‘cholinergic disorder’—evidence that cholinergic–monoaminergic interactions contribute to EEG slowing and dementia. Behav. Brain Res. 2000;115(2):235–249
  14. German DC, Manaye KF, White CL, Woodward DJ, McIntire DD, Smith WK, et al. Disease-specific patterns of locus coeruleus cell loss. Ann. Neurol. 1992;32(5):667–676
  15. German DC, Nelson O, Liang F, Liang CL, Games D. The PDAPP mouse model of Alzheimer's disease: locus coeruleus neuronal shrinkage. J. Comp. Neurol. 2005;492(4):469–476
  16. Goldman G, Coleman PD. Neuron numbers in locus coeruleus do not change with age in Fisher 344 rat. Neurobiol. Aging. 1981;2(1):33–36
  17. Gonzalo-Ruiz A, González I, Sanz-Anquela JM. Effects of beta-amyloid protein on serotoninergic, noradrenergic, and cholinergic markers in neurons of the pontomesencephalic tegmentum in the rat. J. Chem. Neuroanat. 2003;26(3):153–169
  18. Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM. Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease. Neurobiol. Aging. 2007;28(3):327–335
  19. Guerin D, Sacquet J, Mandairon N, Jourdan F, Didier A. Early locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice. Neurobiol. Aging. 2007;
  20. Gundersen HJ. Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson. J. Microsc. 1986;143(Pt 1):3–45
  21. Head E. Combining an antioxidant-fortified diet with behavioral enrichment leads to cognitive improvement and reduced brain pathology in aging canines: strategies for healthy aging. Ann. N. Y. Acad. Sci. 2007;1114:398–406
  22. Head E, Callahan H, Muggenburg BA, Cotman CW, Milgram NW. Visual-discrimination learning ability and beta-amyloid accumulation in the dog. Neurobiol. Aging. 1998;19(5):415–425
  23. Head E, Liu J, Hagen TM, Muggenburg BA, Milgram NW, Ames BN, et al. Oxidative damage increases with age in a canine model of human brain aging. J. Neurochem. 2002;82(2):375–381
  24. Head E, McCleary R, Hahn FF, Milgram NW, Cotman CW. Region-specific age at onset of beta-amyloid in dogs. Neurobiol. Aging. 2000;21(1):89–96
  25. Head E, Mehta R, Hartley J, Kameka M, Cummings BJ, Cotman CW, et al. Spatial learning and memory as a function of age in the dog. Behav. Neurosci. 1995;109(5):851–858
  26. Heneka MT, Ramanathan M, Jacobs AH, Dumitrescu-Ozimek L, Bilkei-Gorzo A, Debeir T, et al. Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice. J. Neurosci. 2006;26(5):1343–1354
  27. Hoogendijk WJ, Pool CW, Troost D, van Zwieten E, Swaab DF. Image analyser-assisted morphometry of the locus coeruleus in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Brain. 1995;118(Pt 1):131–143
  28. Hoogendijk WJ, Sommer IE, Pool CW, Kamphorst W, Hofman MA, Eikelenboom P, et al. Lack of association between depression and loss of neurons in the locus coeruleus in Alzheimer disease. Arch. Gen Psychiatry. 1999;56(1):45–51
  29. Hou Y, White RG, Bobik M, Marks JS, Russell MJ. Distribution of beta-amyloid in the canine brain. Neuroreport. 1997;8(4):1009–1012
  30. Jiao Y, Sun Z, Lee T, Fusco FR, Kimble TD, Meade CA, et al. A simple and sensitive antigen retrieval method for free floating and slide mounted tissue sections. J. Neurosci. Methods. 1999;93:149–162
  31. Jones BE, Beaudet A. Distribution of acetylcholine and catecholamine neurons in the cat brainstem: a choline acetyltransferase and tyrosine hydroxylase immunohistochemical study. J. Comp. Neurol. 1987;261:15–32
  32. Kalinin S, Gavrilyuk V, Polak PE, Vasser R, Zhao J, Heneka MT, et al. Noradrenaline deficiency in brain increases beta-amyloid plaque burden in an animal model of Alzheimer's disease. Neurobiol. Aging. 2007;28(8):1206–1214
  33. Landsberg G, Araujo JA. Behavior problems in geriatric pets. Vet. Clin. North Am. Small Anim. Pract. 2005;35(3):675–698
  34. Lohr JB, Jeste DV. Locus ceruleus morphometry in aging and schizophrenia. Acta Psychiatr. Scand. 1988;77(6):689–697
  35. Manaye KF, McIntire DD, Mann DM, German DC. Locus coeruleus cell loss in the aging human brain: a non-random process. J. Comp. Neurol. 1995;358(1):79–87
  36. Mann DM, Yates PO, Hawkes J. The noradrenergic system in Alzheimer and multi-infarct dementias. J. Neurol. Neurosurg. Psychiatry. 1982;45(2):113–119
  37. Marner L, Soborg C, Pakkenberg B. Increased volume of the pigmented neurons in the locus coeruleus of schizophrenic subjects: a stereological study. J. Psychiatr. Res. 2005;39(4):337–345
  38. Matthews KL, Chen CP, Esiri MM, Keene J, Minger SL, Francis PT. Noradrenergic changes, aggressive behavior, and cognition in patients with dementia. Biol. Psychiatry. 2002;51(5):407–416
  39. Miyawaki K, Nakayama H, Matsuno S, Tamaoka A, Doi K. Three-dimensional and fractal analyses of assemblies of amyloid beta protein subtypes [Abeta40 and Abeta42(43)] in canine senile plaques. Acta Neuropathol. (Berl). 2002;103(3):228–236
  40. Mouton PR, Pakkenberg B, Gundersen HJ, Price DL. Absolute number and size of pigmented locus coeruleus neurons in young and aged individuals. J. Chem. Neuroanat. 1994;7(3):185–190
  41. Nakamura S, Tamaoka A, Sawamura N, Kiatipattanasakul W, Nakayama H, Shoji S, et al. Deposition of amyloid beta protein (A beta) subtypes [A beta 40 and A beta 42(43)] in canine senile plaques and cerebral amyloid angiopathy. Acta Neuropathol. (Berl). 1997;94(4):323–328
  42. Nicoll JA, Yamada M, Frackowiak J, Mazur-Kolecka B, Weller RO. Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer's disease Pro-CAA position statement. Neurobiol. Aging. 2004;25(5):589–597
  43. O’Neil JN, Mouton PR, Tizabi Y, Ottinger MA, Lei DL, Ingram DK, et al. Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice. J. Chem. Neuroanat. 2007;34(3–4):102–107
  44. Ohm TG, Busch C, Bohl J. Unbiased estimation of neuronal numbers in the human nucleus coeruleus during aging. Neurobiol. Aging. 1997;18(4):393–399
  45. Opii WO, Joshi G, Head E, Milgram NW, Muggenburg BA, Klein JB, et al. Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: relevance to Alzheimer's disease. Neurobiol. Aging. 2008;29(1):51–70
  46. Papaioannou N, Tooten PC, van Ederen AM, Bohl JR, Rofina J, Tsangaris T, et al. Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques. Amyloid. 2001;8(1):11–21
  47. Pugliese M, Carrasco JL, Geloso MC, Mascort J, Michetti F, Mahy N. Gamma-aminobutyric acidergic interneuron vulnerability to aging in canine prefrontal cortex. J. Neurosci. Res. 2004;77(6):913–920
  48. Pugliese M, Geloso MC, Carrasco JL, Mascort J, Michetti F, Mahy N. Canine cognitive deficit correlates with diffuse plaque maturation and S100beta (−) astrocytosis but not with insulin cerebrospinal fluid level. Acta Neuropathol. (Berl). 2006;111(6):519–528
  49. Pugliese M, Mascort J, Mahy N, Ferrer I. Diffuse beta-amyloid plaques and hyperphosphorylated tau are unrelated processes in aged dogs with behavioral deficits. Acta Neuropathol. (Berl). 2006;112(2):175–183
  50. Rofina J, van AI, van Ederen AM, Papaioannou N, Yamaguchi H, Gruys E. Canine counterpart of senile dementia of the Alzheimer type: amyloid plaques near capillaries but lack of spatial relationship with activated microglia and macrophages. Amyloid. 2003;10(2):86–96
  51. Rofina JE, van Ederen AM, Toussaint MJ, Secreve M, van der SA, van dMI, et al. Cognitive disturbances in old dogs suffering from the canine counterpart of Alzheimer's disease. Brain Res. 2006;1069(1):216–226
  52. Russell MJ, White R, Patel E, Markesbery WR, Watson CR, Geddes JW. Familial influence on plaque formation in the beagle brain. Neuroreport. 1992;3(12):1093–1096
  53. Satou T, Cummings BJ, Head E, Nielson KA, Hahn FF, Milgram NW, et al. The progression of beta-amyloid deposition in the frontal cortex of the aged canine. Brain Res. 1997;774(1–2):35–43
  54. Siwak CT, Tapp PD, Head E, Zicker SC, Murphey HL, Muggenburg BA, et al. Chronic antioxidant and mitochondrial cofactor administration improves discrimination learning in aged but not young dogs. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2005;29(3):461–469
  55. Siwak CT, Tapp PD, Milgram NW. Effect of age and level of cognitive function on spontaneous and exploratory behaviors in the beagle dog. Learn. Mem. 2001;8(6):317–325
  56. Siwak-Tapp CT, Head E, Muggenburg BA, Milgram NW, Cotman CW. Region specific neuron loss in the aged canine hippocampus is reduced by enrichment. Neurobiol. Aging. 2008;29(1):39–50
  57. Studzinski CM, Araujo JA, Milgram NW. The canine model of human cognitive aging and dementia: pharmacological validity of the model for assessment of human cognitive-enhancing drugs. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2005;29(3):489–498
  58. Swerdlow RH. Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?. Neurobiol. Aging. 2007;28(10):1465–1480
  59. Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with Lewy bodies. J. Neurosci. 2006;26(2):467–478
  60. Tafti M, Nishino S, Liao W, Dement WC, Mignot E. Mesopontine organization of cholinergic and catecholaminergic cell groups in the normal and narcoleptic dog. J. Comp. Neurol. 1997;379:185–197
  61. Tapp PD, Siwak CT, Estrada J, Holowachuk D, Milgram NW. Effects of age on measures of complex working memory span in the beagle dog (Canis familiaris) using two versions of a spatial list learning paradigm. Learn. Mem. 2003;10(2):148–160
  62. Tomlinson BE, Irving D, Blessed G. Cell loss in the locus coeruleus in senile dementia of Alzheimer type. J. Neurol. Sci. 1981;49(3):419–428
  63. Uchida K, Okuda R, Yamaguchi R, Tateyama S, Nakayama H, Goto N. Double-labeling immunohistochemical studies on canine senile plaques and cerebral amyloid angiopathy. J. Vet. Med. Sci. 1993;55(4):637–642
  64. Vijayashankar N, Brody H. A quantitative study of the pigmented neurons in the nuclei locus coeruleus and subcoeruleus in man as related to aging. J. Neuropathol. Exp. Neurol. 1979;38(5):490–497
  65. Watson RE, Wiegand SJ, Clough RW, Hoffman GE. Use of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology. Peptides. 1986;7(1):155–159
  66. Wegiel J, Wisniewski HM, Dziewiatkowski J, Tarnawski M, Dziewiatkowska A, Morys J, et al. Subpopulation of dogs with severe brain parenchymal beta amyloidosis distinguished with cluster analysis. Brain Res. 1996;728(1):20–26
  67. Weller RO, Nicoll JA. Cerebral amyloid angiopathy: pathogenesis and effects on the ageing and Alzheimer brain. Neurol. Res. 2003;25(6):611–616
  68. West MJ. New stereological methods for counting neurons. Neurobiol. Aging. 1993;14(4):275–285
  69. West MJ. Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias. Trends Neurosci. 1999;22(2):51–61
  70. Wisniewski T, Lalowski M, Bobik M, Russell M, Strosznajder J, Frangione B. Amyloid beta 1-42 deposits do not lead to Alzheimer's neuritic plaques in aged dogs. Biochem. J. 1996;313(Pt 2):575–580
  71. Yoshino T, Uchida K, Tateyama S, Yamaguchi I, Nakayama H, Goto N. A retrospective study of canine senile plaques and cerebral amyloid angiopathy. Vet. Pathol. 1996;33:230–234
  72. Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch. Neurol. 2003;60(3):337–341
  73. Zlokovic BV. Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci. 2005;28(4):202–208

PII: S0197-4580(08)00168-1

doi: 10.1016/j.neurobiolaging.2008.05.014

Neurobiology of Aging
Volume 31, Issue 4 , Pages 625-635 , April 2010

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