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.
Similar content being viewed by others
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
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
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
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
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
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
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
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
Croisier E, Graeber MB (2006) Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging concept of primary gliodegeneration. Acta Neuropathol 112:517–530
Eller M, Williams DR (2011) Alpha-synuclein in Parkinson disease and other neurodegenerative disorders. Clin Chem Lab Med 49:403–408
Frotscher M, Jonas P, Sloviter RS (2006) Synapses formed by normal and abnormal hippocampal mossy fibers. Cell Tissue Res 326:361–367
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
Halliday GM, Stevens CH (2011) Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord 26:6–17
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
Jellinger KA (2004) Lewy body-related alpha-synucleinopathy in the aged human brain. J Neural Transm 111:1219–1235
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
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
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
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
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
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
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
Modi PK, Kanungo MS (2010) Age-dependent expression of S100beta in the brain of mice. Cell Mol Neurobiol 30:709–716
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
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
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
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
Ross CA, Poirier MA (2004) Protein aggregation and neurodegenerative disease. Nat Med 10(Suppl):S10–S17
Sarasa M, Pesini P (2009) Natural non-trasgenic animal models for research in Alzheimer’s disease. Curr Alzheimer Res 6:171–178
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
Su X, Federoff HJ, Maguire-Zeiss KA (2009) Mutant alpha-synuclein overexpression mediates early proinflammatory activity. Neurotox Res 16:238–254
Tai HC, Schuman EM (2008) Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat Rev Neurosci 9:826–838
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
Totterdell S, Hanger D, Meredith GE (2004) The ultrastructural distribution of alpha-synuclein-like protein in normal mouse brain. Brain Res 1004:61–72
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
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
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
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
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).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Ji Hyeon Ahn and Joon Ha Park contributed equally to this study.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-012-9873-8