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Apoptosis in dopaminergic neurons of the human substantia nigra during normal aging
P. Anglade, S. Vyas, E.C. Hirsch and Y. Agid
INSERM U289, Hopital de la Salpetriere, Paris, France
Offprint requests to: Dr. P. Anglade, INSEAM U289, Hopital de la Salpetriere, 47 Bd de I'Hopital, 75013 Paris, France
Summary.Morphological and biochemical alterations
have been described in neurons of the aged human brain.
However, the cell death process associated with neuronal
senescence remains to be elucidated. Apoptosis and
autophagic degeneration, two modes of programmed cell
death described in embryogenesis and tissue renewal in
adult, have been observed in nigral dopaminergic
neurons in patients with Parkinson's disease. In the
present study, we made the hypothesis that programmed
cell death may be also involved in the death of nigral
dopaminergic neurons occurring during aging. Cell death
types were defined by morphological criteria identified
at subcellular level. We thus perfonned an ultrastructural
analysis in order to search for apoptotic and autophagic
features in melanized neurons of the substantia nigra in
four normal aged subjects. Morphological characteristics
of apoptosis, such as contact loss with surrounding
tissues, cell shrinkage and chromatin condensation, were
found in 2% of the total number of melanized neurons
analyzed. Although endoplasmic reticulum appeared
normal, mitochondria were markedly shrunken.
Fragments of melanized neurons were found in glial
cells. Autophagic degeneration or necrosis were not
detected in melanized neurons. Signs of oxidative stress,
such as vacuolation of mitochondria, were observed in
melanized neurons devoid of apoptotic features. These
findings demonstrate that apoptosis is involved in cell
death of nigral dopaminergic neurons during normal
aging. Since morphological abnormalities found in this
study, such as marked mitochondrial shrinkage in
apoptotic neurons, were not observed in patients with
Parkinson's disease, the mechanisms underlying
apoptosis may be different in aging and pathology. Histol Histopathol 12, 603-610 (1997)
Key words: Aging, Apoptosis, Dopaminergic neurons,
Substantia nigra, Ultrastructural analysis
DOI: 10.14670/HH-12.603
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