Apoptosis in amyotrophic lateral sclerosis is not restricted to motor neurons. Bcl-2 expression is increased in unaffected post-central gyrus.
We searched for the presence of apoptotic cell death and studied the distribution of bcl-2, an oncoprotein that counteracts apoptosis, in amyotrophic lateral sclerosis (ALS). Brain and spinal cord specimens from 12 ALS patients were compared with those from six non-neurological controls. ALS brain tissue was pre-selected by the presence of reactive cortical damage. Apoptosis was demonstrated by in situ end-labelling of fragmented DNA, a method that is suitable for formalin-fixed, paraffin-embedded tissue. All ALS patients exhibited some apoptosis, eight of them did so in each of the three central nervous system (CNS)-levels studied. Apoptosis was not restricted to the motor system, but also affected other neuronal and non-neuronal CNS elements. Apoptosis corresponded with cell shrinkage, and neuronophagia in Nissl stains and with small Nissl-positive bodies. None of the non-neurological controls showed as much apoptosis as any of the ALS cases. Immunocytochemically, the overall distribution of Bcl-2 did not differ between ALS and non-neurological controls. In ALS, however, we found variable degrees of increased Bcl-2 expressed in the nuclei and in the cytoplasm. We found no inverse relationship between apoptosis and bcl-2 expression.
Troost
D
D
Department of Pathology, Graduate School of Neurosciences Amsterdam, Netherlands.
Aten
J
J
Morsink
F
F
de Jong
J M
JM
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D001344:Autopsy; D002540:Cerebral Cortex / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D009410:Nerve Degeneration; D009474:Neurons / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D012016:Reference Values; D013116:Spinal Cord / Q000473:pathology*
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2