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Synaptophysin in spinal anterior horn in aging and ALS: an immunohistological study

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Summary

Aged-related spinal cord changes such as neuronal loss have been related to the degree of clinical severity of amyotrophic lateral sclerosis (ALS); morphological data on synapses are, however, wanting. Variations in synaptophysin (Sph) expression in aging and ALS were thus studied at the level of lower motor neurons in 40 controls with non-neurological diseases and 11 cases of ALS. Control sections of formalin fixed paraffin embedded cervical (C7/8), thoracic (T10) and lumbar spinal cord (L5) and C6, C7, C8 and L5 of ALS cases were stained with haematoxylin and eosin, luxol fast blue (LFB), and immunostained with a mouse monoclonal antibody against Sph. The neuropil of the anterior horn (AH) in all control cases demonstrated Sph positivity. A dot-like pattern of positivity of presynaptic terminals on soma of motor neurons and fine immunoreactivity along neuronal processes were observed. A significant reduction of Sph immunostaining was observed in the neuropil with increasing age and 3 different somatic patterns were seen: a-well preserved Sph reactivity around the soma and the proximal dendrites of histologically normal neurons; b-few chromatolytic neurons showing large numbers of dot-like presynaptic terminals around the cell body and in a “fused” pattern; c-intense, diffuse, and homogeneous reactivity of some neurons. Attenuation of Sph reactivity in the AH neuropil, to its complete loss, was observed in all ALS cases. In addition to patterns a-c, two additional microscopic findings were noted in ALS: d-chromatolytic neurons showing complete absence of Sph reactivity; e-absence of Sph reactivity around the soma and the proximal dendrites of histologically normal surviving neurons.

Our findings demonstrate that there is a decrease in Sph immunostaining with aging, thus suggesting an alteration in dendritic networks of the AH with aging. Changes in the pattern of Sph immunoreactivity in cell bodies may represent synaptic plasticity and/or degeneration. Reinnervation may also be a possible mechanism as a response to neuronal loss in oldest control cases. Sph reactivity results may thus lend support to the presence of superimposed aging components in ALS cases which may give an insight into explaining the increasing severity of the disease which is encountered with advancing age.

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Author notes

  1. F. F. Cruz-Sánchez

    Present address: Neurological Tissue Bank, Hospital Clinic-University of Barcelona, Spain

Authors and Affiliations

  1. Neurological Tissue Bank, Hospital Clinic-University of Barcelona, Spain

    A. Moral, C. Castejón & E. Tolosa

  2. Walton Centre for Neurology and Neurosurgery, Liverpool, UK

    M. L. Rossi

  3. Epidemiology and Biostatistics Unit, Hospital Clinic-University of Barcelona, Spain

    L. Quintó

  4. Department of Biochemistry, Charing Cross Hospital, London, UK

    J. de Belleroche

Authors
  1. F. F. Cruz-Sánchez
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  2. A. Moral
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  3. M. L. Rossi
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  4. L. Quintó
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  5. C. Castejón
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  6. E. Tolosa
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  7. J. de Belleroche
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Cruz-Sánchez, F.F., Moral, A., Rossi, M.L. et al. Synaptophysin in spinal anterior horn in aging and ALS: an immunohistological study. J. Neural Transmission 103, 1317–1329 (1996). https://doi.org/10.1007/BF01271192

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  • DOI: https://doi.org/10.1007/BF01271192

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