Activated caspase-9 immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy. (15th August 2016)

• Record Type: Journal Article
• Authors: Kawamoto, Yasuhiro; Ayaki, Takashi; Urushitani, Makoto; Ito, Hidefumi; Takahashi, Ryosuke
• Is Part Of: Neuroscience letters. Volume 628(2016)
• Page Start: 207
• Page End: 212
• Publication Date: 2016-08-15
• Subjects: DLB dementia with Lewy bodies -- GCI glial cytoplasmic inclusion -- MSA multiple system atrophy -- MSA-C MSA of the cerebellar type -- MSA-P MSA of the parkinsonian type -- NCI neuronal cytoplasmic inclusion -- PBS phosphate-buffered saline -- PD Parkinson's disease; Apoptosome -- Caspase-9 -- Glial cytoplasmic inclusions -- Multiple system atrophy -- Neuronal cytoplasmic inclusions; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.06.036
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: GCIs and NCIs were intensely immunoractive for cytochrome c, Apaf-1 and caspase-9. Activated caspase-9 immunoreactivity was increased in oligodendrocytes in MSA. GCIs and NCIs were strongly immunoreactive for activated caspase-9. Approximately 80% of GCIs and NCIs were immunopositive for activated caspaae-9. Abstract: The mitochondria play an important role in apoptotic cell death, and the released cytochrome c from the mitochondria promotes the formation of the apoptosome, which contains cytochrome c, Apaf-1 and caspase-9, resulting in the activation of caspase-9 and the promotion of the apoptotic cascade. To investigate the role of mitochondria-dependent apoptotic cell death in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on apoptosome-related proteins in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. We then performed double-labeling immunohistochemistry for activated caspase-9 and α-synuclein in some sections from 10 patients with MSA. In the brains with MSA, glial cytoplasmic inclusions (GCIs) and neuronal cytoplasmic inclusions (NCIs) were intensely immunoreactive for cytochrome c, Apaf-1 and caspase-9. Activated caspase-9 immunoreactivities were also confirmed to be densely localized to both GCIs and NCIs using two types of anti-cleaved caspase-9 antibodies. The semiquantitative analyses using the upper pontine sections double-immunostained with cleaved caspase-9 and α-synuclein demonstrated that approximately 80% of GCIs and NCIs were immunopositive for cleaved caspase-9. Our results suggest that the formation of the apoptosome accompanied by the activation of caspase-9 may occur in brains affected by MSA, and that a mitochondria-dependent apoptotic pathway may be partially associated with the pathogenesis of MSA.