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Is motoneuronal cell death in amyotrophic lateral sclerosis apoptosis?
Author(s) -
Yamazaki Mineo,
Esumi Eisaku,
Nakano Imaharu
Publication year - 2005
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2005.00648.x
Subject(s) - tunel assay , apoptosis , amyotrophic lateral sclerosis , programmed cell death , spinal cord , biology , motor neuron , neuroscience , caspase 3 , caspase , anterior horn cell , dna fragmentation , microbiology and biotechnology , pathology , medicine , biochemistry , disease
To clarify the controversy concerning whether the cell death of motor neurons in ALS is apoptosis, we investigated the expression of Apaf‐1 and caspase‐9 mRNA in spinal cord tissue obained at autopsy from patients with ALS and controls using RT‐PCR; the presence of in situ nuclear DNA fragmentation in motor neurons by the TdT‐mediated dUTP‐biotin nick end‐labeling (TUNEL) method; and immunocytochemical localization of Apaf‐1 and caspase‐3, which are known as promotors of apoptotic processes. Although Apaf‐1 and caspase‐9 mRNAs levels were increased in ALS, Apaf‐1 immunoreactivity (IR) showed no significant difference between ALS and the control, and caspase‐3 IR was not observed in ALS motoneurons, casting doubt on the notion that motor neurons in ALS undergo death by the classic apoptotic pathway. Although TUNEL‐positive motor neurons were frequently observed in the anterior horn in ALS, these neurons always showed an atrophic cell body with a shrunken and pyknotic nucleus, indicating that they were at the terminal stage of degeneration. No apoptotic bodies were seen. These findings suggest that the mechanism of motor neuronal cell death in ALS might not be apoptosis, but some other as yet unidentified mechanism.