Skip to main content
Log in

Dying-back of Purkinje cell dendrites with synapse loss in aging rats

  • Published:
Journal of Neurocytology

Abstract

Qualitative and quantitative changes were found in the cerebellar circuitry of old as compared to young rats. The old group had a reduced number of synapses (at least 30%), however, there was an increase in the size of remaining synaptic components (13.5% for spine head volume, 66% for bouton volume, and 17% for the area of synaptic contact zones). Furthermore, there were pronounced morphological changes in the older group appearing as: 1) prominent lipofuscin bodies in Purkinje cell somata, 2) numerous myelinated fibers in the lower part of the molecular layer, 3) tortuous Purkinje cell dendrites in a thinned molecular layer, and 4) abundant vacuolar profiles and membrane swirls in small and intermediate-sized dendrites. Our findings suggest that Purkinje cell dendrites are dying-back reducing the target field for granule cells and that remaining synaptic sites compensate by increasing synaptic contact area as well as the size of pre- and postsynaptic structures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bercombie, M. (1946) Estimation of nuclear populations from microtome sections. Anatomical Record 94, 239–247.

    Google Scholar 

  • Adams, I. (1987a) Comparison of synaptic changes in the precentral and postcentral cerebral cortex of aging humans: a quantitative ultrastructural study. Neurobiology of Aging 8, 203–212.

    Google Scholar 

  • Adams, I. (1987b) Plasticity of the synaptic contact zone following loss of synapses in the cerebral cortex of aging humans. Brain Research 424, 343–351.

    Google Scholar 

  • Adams, I. & Jones, D. G. (1982) Synaptic remodelling and astrocytic hypertrophy in rat cerebral cortex from early to late adulthood. Neurobiology of Aging 3, 179–186.

    Google Scholar 

  • Bakalian, A., Corman, B., Delhaye-Bouchaud, N. & Mariani, J. (1991) Quantitative analysis of the Purkinje cell population during extreme ageing in the cerebellum of theWistar=Louvain rat. Neurobiology of Aging 12, 425–430.

    Google Scholar 

  • Bertoni-Freddari, C., Giuli, C., Pieri, C. & Paci, D. (1986a) Age-related morphological rearrangements of synaptic junctions in the rat cerebellum and hippocampus. Archives of Gerontology & Geriatrics 5, 297–304.

    Google Scholar 

  • Bertoni-Freddari, C., Giuli, C., Pieri, C. & Paci, D. (1986b) Quantitative investigation of the morphological plasticity of synaptic junctions in rat dentate gyrus during aging. Brain Research 366, 187–192.

    Google Scholar 

  • Brizzee, K. R. (1987) Neurons numbers and dendritic extent in normal aging and AlzheimerÕs disease. Neurobiology of Aging 8, 579–580.

    Google Scholar 

  • Brizzee, K. R. & Ordy, J. M. (1979) Age pigments, cell loss and hippocampal function. Mechanisms of Ageing & Development 9, 143–162.

    Google Scholar 

  • Brizzee, K. R., Ordy, J. M. & Bartus, R. T. (1980) Localization of cellular changes within multimodal sensory regions in aged monkey brain: possible implications for age-related cognitive loss. Neurobiology of Aging 1, 45–52.

    Google Scholar 

  • Chalkley, H. W., Cornfiled, J. & Park, H. (1949) A method for estimating volume-surface ratios. Science 110, 295–297.

    Google Scholar 

  • Chen, S. & Hillman, D. E. (1982) Plasticity of the parallel fiber-Purkinje cell synapse by spine takeover and new synapse formation in the adult rat. Brain Research 240, 205–220.

    Google Scholar 

  • Chien, C. L., Mason, C. A. & Liem, R. K. (1996) Alpha-Internexin is the only neuronal intermediate filament expressed in developing cerebellar granule neurons. Journal of Neurobiogy 29, 304–318.

    Google Scholar 

  • Coleman, P. D. & Flood, D. G. (1986) Dendritic proliferation in the aging brain as a compensatory repair mechanism. [Review]. Progress in Brain Research 70, 227–237.

    Google Scholar 

  • Coleman, P. D. & Flood, D. G. (1987) Neuron numbers and dendritic extent in normal aging and AlzheimerÕs disease. [Review]. Neurobiology of Aging 8, 521–545.

    Google Scholar 

  • Colon, E. J. (1972) The elderly brain. A quantitative analysis in the cerebral cortex of two cases. Psychiatria, Neurologia, Neurochirurgia 75, 261–270.

    Google Scholar 

  • Cotman, C. W. & Scheff, S. W. (1979) Compensatory synapse growth in aged animals after neuronal death. Mechanisms of Ageing & Development 9, 103–117.

    Google Scholar 

  • Cragg, B. G. (1975) The density of synapses and neurons in normal, mentally defective ageing human brains. Brain 98, 81–90.

    Google Scholar 

  • Curcio, C. A. & Hinds, J. W. (1983) Stability of synaptic density and spine volume in dentate gyrus of aged rats. Neurobiology of Aging 4, 77–87.

    Google Scholar 

  • Devaney, K. O. & Johnson, H. A. (1980) Neuron loss in the aging visual cortex of man. Journal of Gerontology 35, 836–841.

    Google Scholar 

  • Dlugos, C. A. & Pentney, R. J. (1994) Morphometric analyses of Purkinje and granule cells in aging F344 rats. Neurobiology of Aging 15, 435–440.

    Google Scholar 

  • Druge, H., Heinsen, H. & Heinsen, Y. L. (1986) Quantitative studies in ageing Chbb:THOM (Wistar) rats. II. Neuron numbers in lobules I, VIb + c and X. Bibliotheca Anatomica 28, 121–137.

    Google Scholar 

  • Fliegner, K. H., Kaplan, M. P., Wood, T. L., Pintar, J. E. & Liem, R. K. (1994) Expression of the gene for the neuronal intermediate filament protein alpha-internexin coincides with the onset of neuronal differentiation in the developing rat nervous system. Journal of Comparative Neurology 342, 161–173.

    Google Scholar 

  • Flood, D. G. & Coleman, P. D. (1988) Neuron numbers and sizes in aging brain: comparisons of human, monkey, and rodent data. [Review]. Neurobiology of Aging 9, 453–463.

    Google Scholar 

  • Forbes, W. B. (1984) Aging-related morphological changes in the main olfactory bulb of the Fischer 344 rat. Neurobiology of Aging 5, 93–99.

    Google Scholar 

  • Gall, C. & Lynch, G. (1978) Rapid axon sprouting in the neonatal rat hippocampus. Brain Research 153, 357–362.

    Google Scholar 

  • Glick, R. & Bondareff, W. (1979) Loss of synapses in the cerebellar cortex of the senescent rat. Journal of Gerontology 34, 818–822.

    Google Scholar 

  • Gundersen, H. J., Bagger, P., Bendtsen, T. F., Evans, S. M., Korbo, L., Marcussen, N. et al. (1988a) The new stereological tools: disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. Apmis 96, 857–881.

    Google Scholar 

  • Gundersen, H. J., Bendtsen, T. F., Korbo, L., Marcussen, N., Moller, A., Nielsen, K. et al. (1988b) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. Apmis 96, 379–394.

    Google Scholar 

  • Hadj-Sahraoui, N., Frederic, F., Zanjani, H., Herrup, K., Delhaye-Bouchaud, N. & Mariani, J. (1997) Purkinje cell loss in heterozygous staggerer mutant mice during aging. Developmental Brain Research 98, 1–8.

    Google Scholar 

  • Hall, T. C., Miller, K. H. & Corsellis, J. A. N. (1975) Variations in human Purkinje cell population according to age and sex. Neuropathology & Applied Neurobiology 1, 267–292.

    Google Scholar 

  • Haug, H., Knebel, G., Mecke, E., Orun, C. & Sass, N. L. (1981) The aging of cortical cytoarchitectonics in the light of stereological investigations. Progress in Clinical & Biological Research 59B, 193–197.

    Google Scholar 

  • Henderson, G., Tomlinson, B. E. & Gibson, P. H. (1980) Cell counts in human cerebral cortex in normal adults throughout life using an image analysing computer. Journal of Neurological Science 46, 113–136.

    Google Scholar 

  • Hillman, D. & Chen, S. (1984a) Constraints on plasticity of cerebellar circuitry. In: Cerebellar Functions (edited by Bloedel, J. R., Dichgans J. & Precht, W.), pp. 300–317, Springer-Verlag.

  • Hillman, D. E. & Chen, S. (1984b) Reciprocal relationship between size of postsynaptic densities and their number: constancy in contact area. Brain Research 295, 325–343.

    Google Scholar 

  • Hillman, D. & Chen, S. (1985a) Plasticity in the size of pre-and postsynaptic membrane specializations. In: Synaptic Plasticity and Remodeling (edited by Cotman, C.), pp. 39–76. New York: Guilford Publ.

    Google Scholar 

  • Hillman, D. E. & Chen, S. (1985b) Compensation in the number of presynaptic dense projections and synaptic vesicles in remaining parallel fibres following cerebellar lesions. Journal of Neurocytology 14, 673–687.

    Google Scholar 

  • Hinds, J. W. & Mcnelly, N. A. (1977) Aging of the rat olfactory bulb: growth and atrophy of constituent layers and changes in size and number of mitral cells. Journal of Comparative Neurology 72, 345–367.

    Google Scholar 

  • Hinds, J. W. & Mcnelly, N. A. (1978) Dispersion of cisternae of rough endoplasmic reticulum in aging CNS neurons: a strictly linear trend. American Journal of Anatomy 152, 433–439.

    Google Scholar 

  • Levine, M. S., Adinolfi, A. M., Fisher, R. S., Hull, C. D., Buchwald, N. A. & Mcallister, J. P. (1986) Quantitative morphology of medium-sized caudate spiny neurons in aged cats. Neurobiology of Aging 7, 277–286.

    Google Scholar 

  • Mani, R. B., Lohr, J. B. & Jeste, D. V. (1986) Hippocampal pyramidal cells and aging in the human: a quantitative study of neuronal loss in sectors CA1 to CA4a. Experimental Neurology 94, 29–40.

    Google Scholar 

  • Mann, D. M., Yates, P. O. & Marcyniuk, B. (1984) Changes in nerve cells of the nucleus basalis of Meynert in AlzheimerÕs disease and their relationship to ageing and to the accumulation of lipofuscin pigment. Mechanisms of Ageing & Development 25, 189–204.

    Google Scholar 

  • Mcgeer, P. L., Mcgeer, E. G., Suzuki, J., Dolman, C. E. & Nagai, T. (1984) Aging, AlzheimerÕs disease, and the cholinergic system of the basal forebrain. Neurology 34, 741–745.

    Google Scholar 

  • Nandy, K. (1981) Morphological changes in the cerebellar cortex of aging Macaca nemestrina. Neurobiology of Aging 2, 61–64.

    Google Scholar 

  • Pakkenberg, B. & Gundersen, H. J. (1989) New stereological method for obtaining unbiased and efficient estimates of total nerve cell number in human brain areas. Exemplified by the mediodorsal thalamic nucleus in schizophrenics. Apmis 97, 677–681.

    Google Scholar 

  • Pentney, R. J. (1986) Quantitative analysis of dendritic networks of Purkinje neurons during aging. Neurobiology of Aging 7, 241–248.

    Google Scholar 

  • Pestronk, A., Drachman, D. B. & Griffin, J. W. (1980) Effects of aging on nerve sprouting and regeneration. Experimental Neurology 70, 65–82.

    Google Scholar 

  • Peters, A., Feldman, M. L. & Vaughan, D. W. (1983) The effect of aging on the neuronal population within area 17 of adult rat cerebral cortex. Neurobiology of Aging 4, 273–282.

    Google Scholar 

  • Peters, A., Morrison, J. H., Rosene, D. L. & Hyman, B. T. (1998) Feature article: are neurons lost from the primate cerebral cortex during normal aging? Cerebral Cortex 8, 295–300.

    Google Scholar 

  • Pyapali, G. K. & Turner, D. A. (1996) aIncreased dendritic extent in hippocampal CA1 neurons from aged F344 rats. Neurobiology of Aging 17, 601–611.

    Google Scholar 

  • Rogers, J., Silver, M. A., Shoemaker, W. J. & Bloom, F. E. (1980) Senescent changes in a neurobiological model system: cerebellar Purkinje cell electrophysiology and correlative anatomy. Neurobiology of Aging 1, 3–11.

    Google Scholar 

  • Sarter, M. (1987) Animal models of brain ageing and dementia. [Review]. Comprehensive Gerontology, Section A, Clinical & Laboratory Sciences 1, 4–15.

    Google Scholar 

  • Scheibel, M. E., Lindsay, R. D., Tomiyasu, U. & Scheibel, A. B. (1976) Progressive dendritic changes in the aginghumanlimbic system. Experimental Neurology 53, 420–430.

    Google Scholar 

  • Sturrock, R. R. (1989a) Age related changes in Purkinje cell number in the cerebellar nodulus of the mouse. Journal für Hirnforschung 30, 757–760.

    Google Scholar 

  • Sturrock, R. R. (1989b) Changes in neuron number in the cerebellar cortex of the ageing mouse. Journal für Hirnforschung 30, 499–503.

    Google Scholar 

  • Sturrock, R. R. (1990) A quantitative histological study of Golgi II neurons and pale cells in different cerebellar regions of the adult and ageing mouse brain. Zeitschrift für Mikroskopisch-Anatomische Forschung 104, 705–714.

    Google Scholar 

  • Swaab, D. F., Fliers, E. & Partiman, T. S. (1985) The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Resarch 342, 37–44.

    Google Scholar 

  • Terry, R. D., Deteresa, R. & Hansen, L. A. (1987) Neocortical cell counts in normal human adult aging. Annals of Neurology 21, 530–539.

    Google Scholar 

  • West, M. J. (1993) New stereological methods for counting neurons. Neurobiology of Aging 14, 275–285.

    Google Scholar 

  • West, M. J., Coleman, P. D., Flood, D. G. & Troncoso, J. C. (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and AlzheimerÕs disease. Lancet 344, 769–772.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, S., Hillman, D.E. Dying-back of Purkinje cell dendrites with synapse loss in aging rats. J Neurocytol 28, 187–196 (1999). https://doi.org/10.1023/A:1007015721754

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007015721754

Keywords

Navigation