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One of their causative genes, <jats:italic>CLN10\/CtsD<\/jats:italic>, encodes cathepsin D, a major lysosomal protease. Central nervous system (CNS)\u2010specific <jats:italic>CtsD<\/jats:italic>\u2010deficient 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\u2010 and 4.6\u2010fold 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\u2010positive 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\u2010positive 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\u2010like structures localized to LAMP1\u2010positive lysosomes in <jats:italic>CtsD<\/jats:italic>\u2010deficient astrocytes. SQSTM1\/p62\u2010positive but LAMP1\u2010negative 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.<\/jats:p>","DOI":"10.1002\/glia.24449","type":"journal-article","created":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T07:01:41Z","timestamp":1691823701000},"page":"2753-2769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>TUNEL<\/scp>\u2010positive structures in activated microglia and <scp>SQSTM1<\/scp>\/p62\u2010positive structures in activated astrocytes in the neurodegenerative brain of a <scp>CLN10<\/scp> mouse model"],"prefix":"10.1002","volume":"71","author":[{"given":"Shun","family":"Mitsui","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Neuropathology Juntendo University Graduate School of Medicine  Tokyo 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