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. 2007 Mar 15;10(1):145–156. doi: 10.1111/j.1582-4934.2006.tb00296.x

Neuroglia in the inferior olivary nucleus during normal aging and Alzheimer's disease

H Lasn 1, B Winblad 1, N Bogdanovic 1,*
PMCID: PMC3933107  PMID: 16563227

Abstract

It is likely that neuronal loss occurs in certain brain regions in Alzheimer's Disease (AD) without any neurofibrillary pathology. In the human principle inferior olivary nucleus (PO), we have shown that neuronal loss is about 34% (Lasn et al. Journal of Alzheimer Disease, 2001; 3: 159–168), but the fate of the neuroglial cells is unknown. Since the unique network of neurons and neuroglial cells and their cohabitation are essential for normal functioning of CNS, we designed a study to estimate the total number of oligodendrocytes and astrocytes in normally aged and AD brains. The study is based on 10 control and 11 AD post-mortem human brains. An unbiased stereological fractionator method was used. We found significant oligodendroglial cell loss (46%) in AD as compared to control brains, while the total number of astrocytes showed a tendency to decrease. It is likely that the ratio of oligodendroglial cells to neurons remains unchanged even in degenerative states, indicating that oligodendroglial cells parallel neuronal loss. Astroglial cells did not increase in total number, but the ratio to neurons was significantly increased due to the neuronal loss. Using a novel unbiased quantitative method, we were able to describe significant oligodendroglial loss in the PO but the pathogenic mechanism behind remains unknown.

Keywords: astrocyte, oligodendrocytes, quantification, stereology, dementia, neurodegeneration

References

  • 1.Esiri MM, Morris JH. The neuropathology of dementia. Cambridge University Press; 1997. pp. 80–111. [Google Scholar]
  • 2.Jellinger KA. Cell death mechanisms in neurodegeneration. J Cell Mol Med. 2001;5:1–17. doi: 10.1111/j.1582-4934.2001.tb00134.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Unger JW. Glial reaction in aging and Alzheimer's Disease. Microsc Res Tech. 1998;43:24–8. doi: 10.1002/(SICI)1097-0029(19981001)43:1<24::AID-JEMT4>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
  • 4.Giannakopoulos P, Hof PR, Bouras C. Selective vulnerability of neocortical association areas in Alzheimer's disease. Microsc Res Tech. 1998;43:16–23. doi: 10.1002/(SICI)1097-0029(19981001)43:1<16::AID-JEMT3>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  • 5.Brun A, Liu X, Erikson C. Synapse loss and gliosis in the molecular layer of the cerebral cortex in Alzheimer's disease and in frontal lobe degeneration. Neurodegeneration. 1995;4:171–7. doi: 10.1006/neur.1995.0021. [DOI] [PubMed] [Google Scholar]
  • 6.Liu X, Erikson C, Brun A. Cortical synaptic changes and gliosis in normal aging, Alzheimer's disease and frontal lobe degeneration. Dementia. 1996;7:128–34. doi: 10.1159/000106867. [DOI] [PubMed] [Google Scholar]
  • 7.Overmyer M, Helisalmi S, Soininen H, Laakso M, Riekkinen P, Alafuzoff I. Astrogliosis and the ApoE Genotype. Dem Ger Cogn Dis. 1999;10:252–7. doi: 10.1159/000017128. [DOI] [PubMed] [Google Scholar]
  • 8.Whitman GT, Cotman CW. Oligodendrocyte degeneration in AD. Neurobiol Aging. 2004;25:33–6. doi: 10.1016/j.neurobiolaging.2003.06.001. [DOI] [PubMed] [Google Scholar]
  • 9.Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59. doi: 10.1007/BF00308809. [DOI] [PubMed] [Google Scholar]
  • 10.Rub U, del Tredici K, Schultz C, Thal DR, Braak E, Braak H. The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology. Acta Neuropathol. (Berl) 2001;101:555–64. doi: 10.1007/s004010000320. [DOI] [PubMed] [Google Scholar]
  • 11.Rüb U, del Tredici K, Schultz C, Thal DR, Braak E, Braak H. The evolution of Alzheimr's disease-related cytoskeletal pathology in the human raphe nuclei. Neuropath Appl Neurobiol. 2000;26:553–67. doi: 10.1046/j.0305-1846.2000.00291.x. [DOI] [PubMed] [Google Scholar]
  • 12.Braak H, del Tredici K. Poor and protracted myelination as a contributory factor to neurodegenerative disorders. Neurobiol Aging. 2004;25:19–23. doi: 10.1016/j.neurobiolaging.2003.04.001. [DOI] [PubMed] [Google Scholar]
  • 13.Lasn H, Winblad B, Bogdanovic N. The number of neurons in the inferior olivary nucleus in Alzheimer's disease and normal aging: A stereological study using the optical fractionator. JAD. 2001;3:159–68. doi: 10.3233/jad-2001-3201. [DOI] [PubMed] [Google Scholar]
  • 14.Bacci A, Verderio C, Pravettoni E, Mateoli M. The role of glial cells in synaptic function. Phil Trans R Soc Lond. 1999;B354:403–9. doi: 10.1098/rstb.1999.0393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Dringer R. Metabolism and functions of glutathione in brain. Prog Neurobiol. 2000;62:649–71. doi: 10.1016/s0301-0082(99)00060-x. [DOI] [PubMed] [Google Scholar]
  • 16.Graeber MB, Blakemore WF, Kreutzberg WG. In: Cellular pathology of the central nervous system. Greenfield Neuropathology, 7th. Graham DI, Lantos P, editors. 2002. pp. 123–92. [Google Scholar]
  • 17.Kirchhoff F, Dringer R, Giaume C. Pathways of neuronastrocyte interactions and their possible role in neuroprotection. Eur Arch Psych Clin Neurosci. 2001;251:159–69. doi: 10.1007/s004060170036. [DOI] [PubMed] [Google Scholar]
  • 18.Martinez G, Carnazza ML, Von Giacomo C, Sorrenti V, Avitabile M, van Ella A. GFAP, S-100β and vimentin proteins in rat after cerebral post-ischemic reperfusion. Int J Neurosci. 1998;16:519–26. doi: 10.1016/s0736-5748(98)00035-5. [DOI] [PubMed] [Google Scholar]
  • 19.Ventura R, Harris KM. Three-dimensional relationships between hippocampal synapses and astrocytes. J Neurosci. 1999;19:6897–906. doi: 10.1523/JNEUROSCI.19-16-06897.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Pakkenberg B, Pelvig D, Marner L, Bundgaard MJ, Gundersen HJG, Nyengaard JR. Regeur L. Aging and the human neocortex. Exp Gerontol. 2003;38:95–9. doi: 10.1016/s0531-5565(02)00151-1. [DOI] [PubMed] [Google Scholar]
  • 21.Pelvig DP, Pakkenberg H, Regeur L, Oster S, Pakkenberg B. Neocortical glial cell numbers in Alzheimer's disease. Dem Ger Cogn Dis. 2003;16:212–9. doi: 10.1159/000072805. [DOI] [PubMed] [Google Scholar]
  • 22.American psychiatric Association. Committee on Nomenclature and Statistics. Diagnostical and statistical manual of mental disorders. 4th. 1994. pp. 133–45. edn . Washington DC. [Google Scholar]
  • 23.McKhann G, Drachmann D, Folstein M, Katzmann R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work group under the auspices of the Department of Health and Human Services; Neurology. 1984;34:939–44. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  • 24.Bogdanovic N, Morris JH. Diagnostic criteria for Alzheimer's disease in multicentre brain banking. In: Cruz-Sanches FF, Ravid R, Cuzner ML, editors. Neuropathological diagnostic criteria for brain banking. IOS press; 1995. pp. 20–9. Amsterdam. [Google Scholar]
  • 25.Mirra SS, Hart MN, Terry RD. Making the diagnosis of Alzheimer's disease. Arch Pathol Lab Med. 1993;117:132–44. [PubMed] [Google Scholar]
  • 26.National Institute on Aging and Reagan Institute Working Group on diagnostic criteriafor the neuropathological assessment of Alzheimer disease. Consensus recommendations for the post-mortem diagnosis of Alzheimer's disease. Neurobiol Aging. 1997;18:S1–2. [PubMed] [Google Scholar]
  • 27.Näslund J, Haroutunian V, Mohs R, Davis KL, Davies P, Greengard P, Buxbaum JD. Correlation between elevated levels of amyloid â-peptide in the brain and cognitive decline. JAMA. 2000;283:1571–7. doi: 10.1001/jama.283.12.1571. [DOI] [PubMed] [Google Scholar]
  • 28.Berry M, Butt AM, Wilkin G, Perry VH. Structure and function of glia in the central nervous system. Greenfield's Neuropathology. 7th 2002. [Google Scholar]
  • 29.Dawson TP, Neal JW, Llewellyn L, Thomas C. Neuropathology techniques. Oxford University press; 2003. pp. 162–79. [Google Scholar]
  • 30.West MJ, Slomianka L, Gundersen HJ. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. The Anat Rec. 1991;231:482–97. doi: 10.1002/ar.1092310411. [DOI] [PubMed] [Google Scholar]
  • 31.Gundersen HJG, Jensen EBV, Kieu K, Nielsen J. The efficiency of systematic sampling in stereology - reconsidered. J Microsc. 1999;193:199–211. doi: 10.1046/j.1365-2818.1999.00457.x. [DOI] [PubMed] [Google Scholar]
  • 32.Gundersen HJ. Stereology of arbritrary particles. A review of unbiased number and size estimators and a presentation of some new ones, in memory of William Thompson. J Microsc. 1986;143:3–45. [PubMed] [Google Scholar]
  • 33.Braak H, Braak E. Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Path. 1991;1:213–6. doi: 10.1111/j.1750-3639.1991.tb00661.x. [DOI] [PubMed] [Google Scholar]
  • 34.Petrova PS, Raibekas A, Pevsner J, Vigo N, Anafi M, Moore MK, Peaire A, Shridhar V, Smith DI, Kelly J, Durocher Y, Commissiong JW. Discovering novel phenotype-selective neurotrophic factors to treat neurodegenerative diseases. Prog Brain Res. 2004;146:168–83. doi: 10.1016/s0079-6123(03)46012-3. [DOI] [PubMed] [Google Scholar]
  • 35.Barres BA, Barde Y-A. Neuronal and glial cell biology. Curr Opin Neurobiol. 2000;10:642–8. doi: 10.1016/s0959-4388(00)00134-3. [DOI] [PubMed] [Google Scholar]
  • 36.Ludwin SK. The pathology of the oligodendrocyte. J Neuropathol Exp Neurol. 1997;56:111–24. doi: 10.1097/00005072-199702000-00001. [DOI] [PubMed] [Google Scholar]
  • 37.Peinado MA. Histology and histochemistry of the aging cerebral cortex: An overview. Microsc Res Tech. 1998;43:1–7. doi: 10.1002/(SICI)1097-0029(19981001)43:1<1::AID-JEMT1>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  • 38.Du Y, Dreyfus CF. Oligodendrocytes as providers of growth factors. J Neurosci Res. 2003;68:647–54. doi: 10.1002/jnr.10245. [DOI] [PubMed] [Google Scholar]
  • 39.Lee JT, Xu J, Lee JM, Ku G, Han X, Yang DI, Chen S, Hsu CY. Amyloid-â peptide induces oligodendrocyte death by activating the neutral sphingomyelinaseceramide pathway. J Cell Biol. 2004;164:123–31. doi: 10.1083/jcb.200307017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Braak H, Braak E. Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol. 1996;92:197–201. doi: 10.1007/s004010050508. [DOI] [PubMed] [Google Scholar]
  • 41.Iseki E, Matsushita M, Kosaka K, Kondo H, Ishii T, Amano N. Distribution and morphology of brain stem plaques in Alzheimer's disease. Acta Neuropath. 1989;78:131–6. doi: 10.1007/BF00688200. [DOI] [PubMed] [Google Scholar]
  • 42.Matsusaka H, Ikeda K, Akiyama H, Arai T, Inoue M, Yagishita S. Astrocytic pathology in progressive supranuclear palsy: significance for neuropathological diagnosis. Acta Neuropathol. 1998;96:248–52. doi: 10.1007/s004010050891. [DOI] [PubMed] [Google Scholar]
  • 43.Ikeda K, Akiyama H, Arai T, Kondo H, Haga C, Iritani S, Tsuchiya K. Alz-50/Gallyas -positive lysosome-like intraneuronal granules in Alzheimer's disease and control brains. Neurosci Lett. 1998;258:113–6. doi: 10.1016/s0304-3940(98)00867-2. [DOI] [PubMed] [Google Scholar]
  • 44.Nixon RA, Cataldo AM, Paskevich CA, Hamilton DJ, Wheelock DR, Kanaley-Andrews L. The lysosomal system in neurons. Involvement at multiple stages of Alzheimer's disease pathogenesis. Ann NY Acad Sci. 1992;674:65–88. doi: 10.1111/j.1749-6632.1992.tb27478.x. [DOI] [PubMed] [Google Scholar]
  • 45.Nixon RA, Cataldo AM, Mathews PM. The endosomal-Lysosomal system of neurons in Alzheimer's disease pathogenesis: A review. Neurochem Res. 2000;25:1161–72. doi: 10.1023/a:1007675508413. [DOI] [PubMed] [Google Scholar]
  • 46.Nixon RA, Mathews PM, Cataldo AM. The neuronal endosomal-lysosomal system in Alzheimer's disease. JAD. 2001;3:97–107. doi: 10.3233/jad-2001-3114. [DOI] [PubMed] [Google Scholar]
  • 47.Cataldo AM, Barnett JL, Mann DM, Nixon RA. Colocalization of lysosomal hydrolase and β-amyloid in duffuse plaques of the cerebellum and striatum in Alzheimer's disease and Down's syndrome. J Neuropathol Exp Neurol. 1996;55:704–15. doi: 10.1097/00005072-199606000-00004. [DOI] [PubMed] [Google Scholar]
  • 48.Cataldo AM, Rebeck GW, Ghetri B, Hulette C, Lippa C, Van Broeckhoven C, Van Duijn C, Cras P, Bogdanovic N, Bird T, Peterhoff C, Nixon R. Endocytic disturbances distinguish among subtypes of Alzheimer's disease and related disorders. Ann Neurol. 2001;50:661–5. [PubMed] [Google Scholar]
  • 49.Probst-Cousin S, Rickert CH, Schmid KW, Gullotta F. Cell death mechanisms in multiple system atrophy. J Neuropathol Exp Neurol. 1998;57:814–21. doi: 10.1097/00005072-199809000-00002. [DOI] [PubMed] [Google Scholar]
  • 50.Rössler M, Zarski R, Bohl J, Ohm TG. Stage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer's disease. Acta Neuropathol. 2002;103:363–9. doi: 10.1007/s00401-001-0475-7. [DOI] [PubMed] [Google Scholar]

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