Glia. 1995 May;14(1):55-64.
Mitochondrial constituents of corpora amylacea and autofluorescent astrocytic inclusions in senescent human brain.
Corpora amylacea (CA) are cytoplasmic inclusions that accumulate in human brain in the course of normal aging, and to an even greater extent, in Alzheimer's disease and other neurodegenerative conditions. In senescent and Alzheimer-diseased
human brains, astrocytes in limbic and periventricular regions exhibit
red autofluorescent inclusions, homologous to Gomori-positive astrocyte
granules previously described in the brains of aging rodents and other
vertebrates. We have shown that Gomori inclusions in situ and in culture
are derived from autophagocytosed mitochondria exhibiting iron-mediated
peroxidase activity.In the human brain,
the autofluorescent inclusions share many properties with CA. Both
types of inclusion progressively accumulate in periventricular regions
with advancing age, are largely astrocytic in origin, and contain
various heat shock proteins and ubiquitin. Using histochemistry in
conjunction with cofocal microscopy, we demonstrated that both CA and
the red autofluorescent granules exhibit non-enzymatic peroxidase
activity and an affinity for CAH and PAS. The only major divergent
histochemical feature between the Gomori-positive astrocyte granules and
CA is the presence of orange-red autofluorescence in the former and the
absence of endogenous fluorescence in the latter
On the basis of numerous shared topographic and histochemical features, we hypothesized that CA are largely derived from autofluorescent (Gomori-positive) astrocyte granules which reside in periventricular regions of the senescent CNS. Immunofluorescent labeling and laser scanning confocal microscopy demonstrated consistent colocalization of the mitochondrial proteins, sulfite oxidase, and heat shock protein 60, to both CA and the autofluorescent astroglial inclusions. In addition, both CA and the autofluorescent astrocyte granules exhibit staining for DNA which colocalizes to mitochondrial antigens and therefore likely represents mitochondrial nucleic acid in dual-labeled preparations. These observations suggest that a) Gomori-positive astrocyte granules in human brain are homologous to those described in rodents, b) Gomori-positive granules may be structural precursors of CA in senescent human brain, and c) in the aging human brain, degenerate mitochondria within periventricular astrocytes give rise to autofluorescent cytoplasmic granules and corpora amylacea.
On the basis of numerous shared topographic and histochemical features, we hypothesized that CA are largely derived from autofluorescent (Gomori-positive) astrocyte granules which reside in periventricular regions of the senescent CNS. Immunofluorescent labeling and laser scanning confocal microscopy demonstrated consistent colocalization of the mitochondrial proteins, sulfite oxidase, and heat shock protein 60, to both CA and the autofluorescent astroglial inclusions. In addition, both CA and the autofluorescent astrocyte granules exhibit staining for DNA which colocalizes to mitochondrial antigens and therefore likely represents mitochondrial nucleic acid in dual-labeled preparations. These observations suggest that a) Gomori-positive astrocyte granules in human brain are homologous to those described in rodents, b) Gomori-positive granules may be structural precursors of CA in senescent human brain, and c) in the aging human brain, degenerate mitochondria within periventricular astrocytes give rise to autofluorescent cytoplasmic granules and corpora amylacea.
- PMID:
- 7615346
- [PubMed - indexed for MEDLINE]
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