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Differences in Doublecortin Immunoreactivity and Protein Levels in the Hippocampal Dentate Gyrus Between Adult and Aged Dogs

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Abstract

Doublecortin (DCX), a microtubule-associated protein, specifically expresses in neuronal precursors. This protein has been used as a marker for neuronal precursors and neurogenesis. In the present study, we observed differences in DCX immunoreactivity and its protein levels in the hippocampal dentate gyrus between adult and aged dogs. In the adult dog, DCX immunoreactive cells with well-stained processes were detected in the subgranular zone of the dentate gyrus. Numbers of DCX immunoreactive cells in the dentate gyrus of the aged dog were significantly decreased compared to those in the adult dog. DCX immunoreactive cells in both adult and aged dog did not show NeuN (a marker for mature neurons) immunoreactivity. NeuN immunoreactivity in the aged dog was poor compared to that in the adult dog. DCX protein level in the aged dentate gyrus was decreased by 80% compared to that in the adult dog. These results suggest that the reduction of DCX in the aged hippocampal dentate gyrus may be involved in some neural deficits related to the hippocampus.

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References

  1. Altman J (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–336

    Article  PubMed  CAS  Google Scholar 

  2. Biebl M, Cooper CM, Winkler J, Kuhn HG (2000) Analysis of neurogenesis and programmed cell death reveals a self-renewing capacity in the adult rat brain. Neurosci Lett 291:17–20

    Article  PubMed  CAS  Google Scholar 

  3. Larsson A, Wilhelmsson U, Pekna M, Pekny M (2004) Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(−/−)Vim(−/−) mice. Neurochem Res 29:2069–2073

    Article  PubMed  CAS  Google Scholar 

  4. Zhu LL, Zhao T, Li HS, Zhao H, Wu LY, Ding AS, Fan WH, Fan M (2005) Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res 1055:1–6

    Article  PubMed  CAS  Google Scholar 

  5. Kanagawa T, Fukuda H, Tsubouchi H, Komoto Y, Hayashi S, Fukui O, Shimoya K, Murata Y (2006) A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat. Brain Res 1111:36–40

    Article  PubMed  CAS  Google Scholar 

  6. Brown JP, Couillard-Despres S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003) Transient expression of doublecortin during adult neurogenesis. J Comp Neurol 467:1–10

    Article  PubMed  CAS  Google Scholar 

  7. Bonfanti L, Theodosis DT (1994) Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb. Neuroscience 62:291–305

    Article  PubMed  CAS  Google Scholar 

  8. Jin K, Mao XO, Greenberg DA (2004) Proteomic analysis of neuronal hypoxia in vitro. Neurochem Res 29:1123–1128

    Article  PubMed  CAS  Google Scholar 

  9. Karl C, Couillard-Després S, Prang P, Munding M, Kilb W, Brigadski T, Plotz S, Mages W, Luhmann H, Winkler J, Bogdahn U, Aigner L (2005) Neuronal precursor-specific activity of a human doublecortin regulatory sequence. J Neurochem 92:264–282

    Article  PubMed  CAS  Google Scholar 

  10. Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell SK, Berwald-Netter Y, Denoulet P, Chelly J (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23:247–256

    Article  PubMed  CAS  Google Scholar 

  11. Gleeson JG, Lin PT, Flanagan LA, Walsh CA (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23:257–271

    Article  PubMed  CAS  Google Scholar 

  12. Capes-Davis A, Tolhurst O, Dunn JM, Jeffrey PL (2005) Expression of doublecortin (DCX) and doublecortin-like kinase (DCLK) within the developing chick brain. Dev Dyn 232:457–467

    Article  PubMed  CAS  Google Scholar 

  13. Rao MS, Shetty AK (2004) Efficacy of doublecortin as a marker to analyse the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus. Eur J Neurosci 19:234–246

    Article  PubMed  Google Scholar 

  14. Nacher J, Crespo C, McEwen BS (2001) Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 14:629–644

    Article  PubMed  CAS  Google Scholar 

  15. Yang HK, Sundholm-Peters NL, Goings GE, Walker AS, Hylandm K, Szele FG (2004) Distribution of doublecortin expressing cells near the lateral ventricles in the adult mouse brain. J Neurosci Res 76:282–295

    Article  PubMed  CAS  Google Scholar 

  16. Patronek GJ, Waters DJ, Glickman LT (1997) Comparative longevity of pet dogs and humans: implications for gerontology research. J Gerontol Series A – Biol Sci Med Sci 52:B171–B178

    CAS  Google Scholar 

  17. Michell AR (1999) Longevity of British breeds of dog and its relationships with sex, size, cardiovascular variables and disease. Vet Record 145:625–629

    CAS  Google Scholar 

  18. Egenvall A, Bonnett BN, Shoukri M, Olson P, Hedharmmar A, Dohoo I (2000) Age pattern of mortality in eight breeds of insured dogs in Sweden. Preventive Vet Med 46:1–14

    Article  CAS  Google Scholar 

  19. Mattson MP (2003) Adventures in neural plasticity, aging, and neurodegenerative disorders aboard the CWC beagle. Neurochem Res 28:1631–1637

    Article  PubMed  CAS  Google Scholar 

  20. Milgram NW (2003) Cognitive experience and its effect on age-dependent cognitive decline in beagle dogs. Neurochem Res 28:1677–1682

    Article  PubMed  CAS  Google Scholar 

  21. Proschowsky HF, Rugbjerg H, Ersboll AK (2003) Mortality of purebred are mixed-breed dogs in Denmark. Preventive Vet Med 58:63–74

    Article  Google Scholar 

  22. Selkoe DJ, Bell DS, Podisny MB, Price DL, Cork LC (1987) Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer’s disease. Science 235:873–877

    Article  PubMed  CAS  Google Scholar 

  23. Johnstone EM, Chaney MO, Norris FH, Pascual R, Little SP (1991) Conservation of the sequence of the Alzheimer’s disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis. Brain Res Mol Brain Res 10:299–305

    Article  PubMed  CAS  Google Scholar 

  24. London ED, Ohata M, Takei H, French AWM, Rapoport I (1983) Regional cerebral metabolic rate for glucose in beagle dogs of different ages. Neurobiol Aging 4:121–126

    Article  PubMed  CAS  Google Scholar 

  25. Su MY, Head E, Brooks WM, Wang Z, Muggenberg BA, Adam GE, Sutherland RJ, Cotman CW, Nalcioglu O (1998) MR imaging of anatomic and vascular characteristics in a canine model of human aging. Neurobiol Aging 9:479–485

    Article  Google Scholar 

  26. Head E, Torp R (2002) Insights into Aβ and presenilin from a canine model of human brain aging. Neurobiol Dis 9:1–10

    Article  PubMed  CAS  Google Scholar 

  27. Cummings BJ, Head E, Ruehl WW, Milgram NW, Cotman CW (1996) The canine as an animal model of human aging and dementia. Neurobiol Aging 17:259–268

    Article  PubMed  CAS  Google Scholar 

  28. Wisniewski T, Lalowski M, Bobik M, Russell M, Strosznajder J, Frangione B (1996) Amyloid beta 1–42 deposits do not lead to Alzheimer’s neuritic plaques in aged dogs. Biochem J 313:575–580

    PubMed  CAS  Google Scholar 

  29. Nakamura S, Tamaoka A, Sawamura N, Kiatipattanasakul W, Nakayama H, Shoji S, Yoshikawa Y, Doi K (1997) Deposition of amyloid β protein (Aβ) subtypes [Aβ40 and Aβ42(43)] in canine senile plaques and cerebral amyloid angiopathy. Acta Neuropathol 94:323–328

    Article  PubMed  CAS  Google Scholar 

  30. Yamada M, Onodera M, Mizuno Y, Mochizuki H (2004) Neurogenesis in olfactory bulb identified by retroviral labeling in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated adult mice. Neuroscience 124:173–181

    Article  PubMed  CAS  Google Scholar 

  31. Cooper-Kuhn CM, Kuhn HG (2002) Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain. Dev Brain Res 134:13–21

    Article  CAS  Google Scholar 

  32. Seki T, Arai Y (1995) Age-related production of new granule cells in the adult dentate gyrus. NeuroReport 6:2479–2482

    Article  PubMed  CAS  Google Scholar 

  33. Kuhn HG, Dickinson-Anson H, Gage F (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16:2027–2033

    PubMed  CAS  Google Scholar 

  34. Kempermann G, Kuhn HG, Gage FH (1998) Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci 18:3206–3212

    PubMed  CAS  Google Scholar 

  35. Cameron H, KcKay RDG (1999) Restoring production of hippocampal neurons in old age. Nat Neurosci 2:894–897

    Article  PubMed  CAS  Google Scholar 

  36. Nacher J, Alonso-Llosa GA, Rosell DR, McEwan BS (2003) NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus. Neurobiol Aging 24:273–284

    Article  PubMed  CAS  Google Scholar 

  37. Heine VM, Maslam S, Joels M, Lucassen PJ (2004) Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus. In absence of an age-related hypothalamus-pituitary-adrenal axis activation. Neurobiol Aging 25:361–375

    Article  PubMed  CAS  Google Scholar 

  38. Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN (2003) Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci USA 100:14385–14390

    Article  PubMed  CAS  Google Scholar 

  39. Snyder JS, Hong N, McDonald RJ, Wojtowicz JM (2005) A role for adult hippocampal neruogenesis in spatial long-term memory. Neuroscience 130:843–852

    Article  PubMed  CAS  Google Scholar 

  40. Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA (1998) Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92:63–72

    Article  PubMed  CAS  Google Scholar 

  41. Des Portes V, Pinard JM, Billuart P, Vinet MC, Koulakoff A, Carrie A, Gelot A, Dupuis E, Motte J, Berwald-Netter Y, Catala M, Kahn A, Beldjord C, Chelly J (1998) A novel CNS gene required for neuronal migration and involved in X-liked subcortical laminar heterotopia and lissencephaly syndrome. Cell 92:51–61

    Article  PubMed  CAS  Google Scholar 

  42. Couillard-Després S, Winkler J, Uyanik G, Aigner L (2001) Molecular mechanisms of neuronal migration disorders, quo vadis? Curr Mol Med 1:677–688

    Article  PubMed  Google Scholar 

  43. Corbo JC, Deuel TA, Long JM, LaPorte P, Tsai E, Wynshaw-Boris A, Walsh CS (2002) Doublecortin is required in mice for lamination of the hippocampus but not the neocortex. J Neurosci 22:7548–7557

    PubMed  CAS  Google Scholar 

  44. Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH (2003) Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development 130:391–339

    Article  PubMed  CAS  Google Scholar 

  45. Kronenberg G, Reuter K, Steiner B et al (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463

    Article  PubMed  Google Scholar 

  46. Wen PH, Friedrich VL Jr, Shioi J, Robakis NK, Elder GA (2002) Presenilin-1 is expressed in neural progenitor cells in the hippocampus of adult mice. Neurosci Lett 318:53–56

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Mr. Seok Han, Mr. Seung Uk Lee and Ms. Hyun Sook Kim for their technical help in this study. This work was supported by the Nano/Bio program of Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. M10641450002-06N4145-00200).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    In Koo Hwang, Jung Hoon Choi & In Se Lee

  2. Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea

    Ki-Yeon Yoo, Hua Li & Moo Ho Won

  3. Department of Biochemistry, College of Sciences, Yonsei University, Seoul, 120-749, South Korea

    Young-Guen Kwon

  4. The Heart Center of Chonnam National University Hospital 8 Hak Dong, Dong Ku, Gwangju, 501-757, South Korea

    Youngkeun Ahn

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  1. In Koo Hwang
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Correspondence to Moo Ho Won.

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Hwang, I.K., Yoo, KY., Li, H. et al. Differences in Doublecortin Immunoreactivity and Protein Levels in the Hippocampal Dentate Gyrus Between Adult and Aged Dogs. Neurochem Res 32, 1604–1609 (2007). https://doi.org/10.1007/s11064-007-9366-1

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