Individual variability in the structural properties of neurons in the human inferior olive
The inferior olive (IO) is the sole source of the climbing fibers innervating the cerebellar cortex. We have previously shown both individual differences in the size and folding pattern of the principal nucleus (IOpr) in humans as well as in the expression of different proteins in IOpr neurons. This high degree of variability was not present in chimpanzee samples. The neurochemical differences might reflect static differences among individuals, but might also reflect age-related processes resulting in alterations of protein synthesis. Several observations support the latter idea. First, accumulation of lipofuscin, the “age pigment” is well documented in IOpr neurons. Second, there are silver- and abnormal tau-immunostained intraneuronal granules in IOpr neurons (Ikeda et al. Neurosci Lett 258:113–116, 1998). Finally, Olszewski and Baxter (Cytoarchitecture of the human brain stem, Second edn. Karger, Basel, 1954) observed an apparent loss of IOpr neurons in older individuals. We have further investigated the possibility of age-related changes in IOpr neurons using silver- and immunostained sections. We found silver-labeled intraneuronal granules in neurons of the IOpr in all human cases studied (n = 17, ages 25–71). We did not, however, confirm immunostaining with antibodies to abnormal tau. There was individual variability in the density of neurons as well as in the expression of the calcium-binding protein calretinin. In the chimpanzee, there were neither silver-stained intraneuronal granules nor irregularities in immunostaining. Overall, the data support the hypothesis that in some, but not all, humans there are functional changes in IOpr neurons and ultimately cell death. Neurochemical changes of IOpr neurons may contribute to age-related changes in motor and cognitive skills mediated by the cerebellum.
KeywordsCerebellar cortex Purkinje cells Aging Climbing fibers Lysosomes Lipofuscin Hyperphosphorylated tau protein Tauopathies
We are grateful to Matthew Stone, Yaechan Choi and Jessica Kichigin for help with immunohistochemistry and the plotting of IOpr sections. Supported in part by the Department of Physiology and Biophysics, University at Buffalo. We thank the National Chimpanzee Brain Resource, NS092988, for the chimpanzee brainstems.
- Adhami F, Liao G, Morozov YM, Schloemer A, Schmithorst VJ, Lorenz JN, Dunn RS, Vorhees CV, Wills-Karp M, Degen JL, Davis RJ, Mizushima N, Rakic P, Dardzinski BJ, Holland SK, Sharp FR, Kuan CY (2006) Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy. Am J Pathol 169:566–583CrossRefPubMedPubMedCentralGoogle Scholar
- Baizer JS, Wong KM, Hof PR, Witelson SF, Sherwood CC (2013c) Degeneration of neurons in the principal nucleus of the inferior olive of the human: evidence from silver staining. Neuroscience Meeting Planner San Diego, CA Society for Neuroscience, 2013 Online Program No. 469.16Google Scholar
- Brody H (1976) An examination of cerebral cortex and brainstem aging. In: Terry R (ed) Neurobiology of aging. Raven, New York, pp 177–181Google Scholar
- Castellani R, Alexiev B, Phillips D, Perry G, Smith M (2007) Microscopic investigations in neurodegenerative diseases. In: Mendez-Vilas A, Diaz J (eds) Modern research and educational topics in microscopy. Formatex, Spain, pp 171–182Google Scholar
- de Silva R, Lashley T, Gibb G, Hanger D, Hope A, Reid A, Bandopadhyay R, Utton M, Strand C, Jowett T, Khan N, Anderton B, Wood N, Holton J, Revesz T, Lees A (2003) Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies. Neuropathol Appl Neurobiol 29:288–302CrossRefPubMedGoogle Scholar
- Gilissen EP, Leroy K, Yilmaz Z, Kovari E, Bouras C, Boom A, Poncelet L, Erwin JM, Sherwood CC, Hof PR, Brion JP (2014) A neuronal aging pattern unique to humans and common chimpanzees. Brain Struct FunctGoogle Scholar
- Jicha GA, Petersen RC, Knopman DS, Boeve BF, Smith GE, Geda YE, Johnson KA, Cha R, Delucia MW, Braak H, Dickson DW, Parisi JE (2006) Argyrophilic grain disease in demented subjects presenting initially with amnestic mild cognitive impairment. J Neuropathol Exp Neurol 65:602–609CrossRefPubMedGoogle Scholar
- LaBossiere E, Glickstein M (1976) Histological processing for the neural sciences. Charles C. Thomas, SpringfieldGoogle Scholar
- Olszewski J, Baxter D (1954) Cytoarchitecture of the human brain stem. 2nd edn. Karger, BaselGoogle Scholar
- Sternfeld M, Shoham S, Klein O, Flores-Flores C, Evron T, Idelson GH, Kitsberg D, Patrick JW, Soreq H (2000) Excess “read-through” acetylcholinesterase attenuates but the “synaptic” variant intensifies neurodeterioration correlates. Proc Natl Acad Sci USA 97:8647–8652CrossRefPubMedPubMedCentralGoogle Scholar