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Comparison of Alpha-Synuclein Immunoreactivity in the Hippocampus Between the Adult and Aged Beagle Dogs

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Abstract

Alpha-synuclein (α-syn), as a neuroprotein, is expressed in neural tissue, and it is related to a synaptic transmission and neuronal plasticity. In this study, we compared the distribution and immunoreactivity of α-syn and related gliosis in hippocampus between young adult (2–3 years) and aged (10–12 years) beagle dogs. In both groups, α-syn immunoreactivity was detected in neuropil of all the hippocampal sub-regions, but not in neuronal somata. In the aged hippocampus, α-syn immunoreactivity was apparently increased in mossy fibers compared to that in the adult dog. In addition, α-syn protein level was markedly increased in the aged hippocampus. On the other hand, GFAP and Iba-1 immunoreactivity in astrocytes and microglia, respectively, were increased in all the hippocampal sub-regions of the aged group compared to that in the adult group: especially, their immunoreactivity was apparently increased around mossy fibers. In addition, in this study, we could not find any expression of α-syn in astrocytes and microglia. These results indicate that α-syn immunoreactivity apparently increases in the aged hippocampus and that GFAP and Iba-1 immunoreactivity are also apparently increased at the regions with increased α-syn immunoreactivity. This increase in α-syn expression might be a feature of normal aging.

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References

  • Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A (2000) Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25:239–252

    Article  PubMed  CAS  Google Scholar 

  • Adamczyk A, Solecka J, Strosznajder JB (2005) Expression of alpha-synuclein in different brain parts of adult and aged rats. J Physiol Pharmacol 56:29–37

    PubMed  CAS  Google Scholar 

  • Alvarez-Garcia O, Vega-Naredo I, Sierra V, Caballero B, Tomas-Zapico C, Camins A, Garcia JJ, Pallas M, Coto-Montes A (2006) Elevated oxidative stress in the brain of senescence-accelerated mice at 5 months of age. Biogerontology 7:43–52

    Article  PubMed  CAS  Google Scholar 

  • Balu M, Sangeetha P, Murali G, Panneerselvam C (2005) Age-related oxidative protein damages in central nervous system of rats: modulatory role of grape seed extract. Int J Dev Neurosci 23:501–507

    Article  PubMed  CAS  Google Scholar 

  • Berry A, Greco A, Giorgio M, Pelicci PG, de Kloet R, Alleva E, Minghetti L, Cirulli F (2008) Deletion of the lifespan determinant p66(Shc) improves performance in a spatial memory task, decreases levels of oxidative stress markers in the hippocampus and increases levels of the neurotrophin BDNF in adult mice. Exp Gerontol 43:200–208

    Article  PubMed  CAS  Google Scholar 

  • Caballero B, Vega-Naredo I, Sierra V, Huidobro-Fernandez C, Soria-Valles C, De Gonzalo-Calvo D, Tolivia D, Gutierrez-Cuesta J, Pallas M, Camins A, Rodriguez-Colunga MJ, Coto-Montes A (2008) Favorable effects of a prolonged treatment with melatonin on the level of oxidative damage and neurodegeneration in senescence-accelerated mice. J Pineal Res 45:302–311

    Article  PubMed  CAS  Google Scholar 

  • Chu Y, Kordower JH (2007) Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: is this the target for Parkinson’s disease? Neurobiol Dis 25:134–149

    Article  PubMed  CAS  Google Scholar 

  • Cotman CW, Head E (2008) The canine (dog) model of human aging and disease: dietary, environmental and immunotherapy approaches. J Alzheimers Dis 15:685–707

    PubMed  CAS  Google Scholar 

  • Croisier E, Graeber MB (2006) Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging concept of primary gliodegeneration. Acta Neuropathol 112:517–530

    Article  PubMed  Google Scholar 

  • Eller M, Williams DR (2011) Alpha-synuclein in Parkinson disease and other neurodegenerative disorders. Clin Chem Lab Med 49:403–408

    Article  PubMed  CAS  Google Scholar 

  • Frotscher M, Jonas P, Sloviter RS (2006) Synapses formed by normal and abnormal hippocampal mossy fibers. Cell Tissue Res 326:361–367

    Article  PubMed  Google Scholar 

  • George JM (2002) The synucleins. Genome Biol 3:REVIEWS3002

  • Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H (2010) Astrocytic expression of Parkinson’s disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain 3:12

    Article  PubMed  Google Scholar 

  • Halliday GM, Stevens CH (2011) Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord 26:6–17

    Article  PubMed  Google Scholar 

  • He WB, Zhang JL, Hu JF, Zhang Y, Machida T, Chen NH (2008) Effects of glucocorticoids on age-related impairments of hippocampal structure and function in mice. Cell Mol Neurobiol 28:277–291

    Article  PubMed  CAS  Google Scholar 

  • Jellinger KA (2004) Lewy body-related alpha-synucleinopathy in the aged human brain. J Neural Transm 111:1219–1235

    Article  PubMed  CAS  Google Scholar 

  • Klegeris A, Giasson BI, Zhang H, Maguire J, Pelech S, McGeer PL (2006) Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells. FASEB J 20:2000–2008

    Article  PubMed  CAS  Google Scholar 

  • Kontopoulos E, Parvin JD, Feany MB (2006) Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 15:3012–3023

    Article  PubMed  CAS  Google Scholar 

  • Kramer ML, Schulz-Schaeffer WJ (2007) Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 27:1405–1410

    Article  PubMed  CAS  Google Scholar 

  • Kudo K, Wati H, Qiao C, Arita J, Kanba S (2005) Age-related disturbance of memory and CREB phosphorylation in CA1 area of hippocampus of rats. Brain Res 1054:30–37

    Article  PubMed  CAS  Google Scholar 

  • Lee HJ, Kim C, Lee SJ (2010a) Alpha-synuclein stimulation of astrocytes: potential role for neuroinflammation and neuroprotection. Oxid Med Cell Longev 3:283–287

    Article  PubMed  Google Scholar 

  • Lee HJ, Suk JE, Patrick C, Bae EJ, Cho JH, Rho S, Hwang D, Masliah E, Lee SJ (2010b) Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 285:9262–9272

    Article  PubMed  CAS  Google Scholar 

  • Lim Y, Kehm VM, Lee EB, Soper JH, Li C, Trojanowski JQ, Lee VM (2011) Alpha-Syn suppression reverses synaptic and memory defects in a mouse model of dementia with Lewy bodies. J Neurosci 31:10076–10087

    Article  PubMed  CAS  Google Scholar 

  • Modi PK, Kanungo MS (2010) Age-dependent expression of S100beta in the brain of mice. Cell Mol Neurobiol 30:709–716

    Article  PubMed  CAS  Google Scholar 

  • Okabayashi S, Kimura N (2007) Immunohistochemical and biochemical analyses of LGI3 in monkey brain: LGI3 accumulates in aged monkey brains. Cell Mol Neurobiol 27:819–830

    Article  PubMed  CAS  Google Scholar 

  • Paramanik V, Thakur MK (2010) Interaction of estrogen receptor associated protein (ERAP) 140 with ER beta decreases but its expression increases in aging mouse cerebral cortex. Cell Mol Neurobiol 30:961–966

    Article  PubMed  CAS  Google Scholar 

  • Probst A, Bloch A, Tolnay M (2008) New insights into the pathology of Parkinson’s disease: does the peripheral autonomic system become central? Eur J Neurol 15(Suppl 1):1–4

    Article  PubMed  Google Scholar 

  • Rampello L, Cerasa S, Alvano A, Butta V, Raffaele R, Vecchio I, Cavallaro T, Cimino E, Incognito T, Nicoletti F (2004) Dementia with Lewy bodies: a review. Arch Gerontol Geriatr 39:1–14

    Article  PubMed  CAS  Google Scholar 

  • Ross CA, Poirier MA (2004) Protein aggregation and neurodegenerative disease. Nat Med 10(Suppl):S10–S17

    Article  PubMed  Google Scholar 

  • Sarasa M, Pesini P (2009) Natural non-trasgenic animal models for research in Alzheimer’s disease. Curr Alzheimer Res 6:171–178

    Article  PubMed  CAS  Google Scholar 

  • Siwak-Tapp CT, Head E, Muggenburg BA, Milgram NW, Cotman CW (2008) Region specific neuron loss in the aged canine hippocampus is reduced by enrichment. Neurobiol Aging 29:39–50

    Article  PubMed  Google Scholar 

  • Su X, Federoff HJ, Maguire-Zeiss KA (2009) Mutant alpha-synuclein overexpression mediates early proinflammatory activity. Neurotox Res 16:238–254

    Article  PubMed  CAS  Google Scholar 

  • Tai HC, Schuman EM (2008) Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat Rev Neurosci 9:826–838

    Article  PubMed  CAS  Google Scholar 

  • Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH, Schinder AF (2008) Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci 11:901–907

    Article  PubMed  CAS  Google Scholar 

  • Totterdell S, Hanger D, Meredith GE (2004) The ultrastructural distribution of alpha-synuclein-like protein in normal mouse brain. Brain Res 1004:61–72

    Article  PubMed  CAS  Google Scholar 

  • Yamada K, Matsukawa N, Yuasa H, Hattori M, Nakazawa H, Borlongan CV, Ojika K (2007) Differential expression of HCNP-related antigens in hippocampus in senescence-accelerated mice. Brain Res 1158:169–175

    Article  PubMed  CAS  Google Scholar 

  • Yokota O, Tsuchiya K, Uchihara T, Ujike H, Terada S, Takahashi M, Kimura Y, Ishizu H, Akiyama H, Kuroda S (2007) Lewy body variant of Alzheimer’s disease or cerebral type lewy body disease? Two autopsy cases of presenile onset with minimal involvement of the brainstem. Neuropathology 27:21–35

    Article  PubMed  Google Scholar 

  • Yu DF, Wu PF, Fu H, Cheng J, Yang YJ, Chen T, Long LH, Chen JG, Wang F (2011) Aging-related alterations in the expression and distribution of GluR2 and PICK1 in the rat hippocampus. Neurosci Lett 497:42–45

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, Wilson B, Zhou Y, Hong JS, Zhang J (2005) Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J 19:533–542

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Mr. Seung Uk Lee for their technical help in this study. This work was supported by and by the Technology Innovation Program funded by the Ministry of Knowledge Economy (MKE, Korea), and by the Regional Core Research Program funded by the Korea Ministry of Education, Science and Technology (Medical & Bio-material Research Center).

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Correspondence to Hyung-Cheul Shin or Moo-Ho Won.

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Ji Hyeon Ahn and Joon Ha Park contributed equally to this study.

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Ahn, J.H., Park, J.H., Yan, B.C. et al. Comparison of Alpha-Synuclein Immunoreactivity in the Hippocampus Between the Adult and Aged Beagle Dogs. Cell Mol Neurobiol 33, 75–84 (2013). https://doi.org/10.1007/s10571-012-9873-8

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  • DOI: https://doi.org/10.1007/s10571-012-9873-8

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