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• W4385778908 abstract "Neuronal ceroid lipofuscinosis is a group of pediatric neurodegenerative diseases. One of their causative genes, CLN10/CtsD, encodes cathepsin D, a major lysosomal protease. Central nervous system (CNS)-specific CtsD-deficient mice exhibit a neurodegenerative disease phenotype with accumulation of ceroid lipofuscins, granular osmiophilic deposits, and SQSTM1/p62. We focused on activated astrocytes and microglia in this neurodegenerative mouse brain, since there are few studies on the relationship between these accumulators and lysosomes in these glial cells. Activated microglia and astrocytes in this mouse thalamus at p24 were increased by approximately 2.5- and 4.6-fold compared with the control, while neurons were decreased by approximately half. Granular osmiophilic deposits were detected in microglial cell bodies and extended their processes in the thalamus. LAMP1-positive lysosomes, but not SQSTM1/p62 aggregates, accumulated in microglia of this mouse thalamus, whereas both lysosomes and SQSTM1/p62 aggregates accumulated in its astrocytes. TUNEL-positive signals were observed mainly in microglia, but few were observed in neurons and astrocytes. These signals were fragmented DNA from degenerated neurons engulfed by microglia or in the lysosomes of microglia. Abnormal autophagic vacuoles also accumulated in the lysosomes of microglia. Granular osmiophilic deposit-like structures localized to LAMP1-positive lysosomes in CtsD-deficient astrocytes. SQSTM1/p62-positive but LAMP1-negative membranous structures also accumulated in the astrocytes and were less condensed than typical granular osmiophilic deposits. These results suggest that CtsD deficiency leads to intracellular abnormalities in activated microglia and astrocytes in addition to neuronal degeneration." @default.
• W4385778908 created "2023-08-13" @default.
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• W4385778908 date "2023-08-12" @default.
• W4385778908 modified "2023-10-15" @default.
• W4385778908 title "<scp>TUNEL</scp>‐positive structures in activated microglia and <scp>SQSTM1</scp>/p62‐positive structures in activated astrocytes in the neurodegenerative brain of a <scp>CLN10</scp> mouse model" @default.
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• W4385778908 doi "https://doi.org/10.1002/glia.24449" @default.
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• W4385778908 hasPublicationYear "2023" @default.
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