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Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red+deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. © 2016 Wiley Periodicals, Inc.

Registro:

Documento: Artículo
Título:Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization
Autor:Pomilio, C.; Pavia, P.; Gorojod, R.M.; Vinuesa, A.; Alaimo, A.; Galvan, V.; Kotler, M.L.; Beauquis, J.; Saravia, F.
Filiación:Departamento De Quimica Biologica, Facultad De Ciencias Exactas Y Naturales, Universidad De Buenos Aires, Instituto De Biologia Y Medicina Experimental Conicet, Buenos Aires, Argentina
Departamento De Quimica Biologica, Facultad De Ciencias Exactas Y Naturales, Universidad De Buenos Aires, IQUIBICEN-Conicet, Buenos Aires, Argentina
Department of Physiology, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, United States
Palabras clave:AD; Astrocytes; Hilus; LC3; Microglia; Neuroinflammation; Stratum radiatum; Ubiquitin; amyloid beta protein; cell protein; congo red; Iba1 protein; protein p62; ubiquitin; unclassified drug; amyloid beta protein; Alzheimer disease; amyloid plaque; animal cell; animal experiment; animal model; animal tissue; Article; astrocyte; autophagy; cell density; cell volume; controlled study; dentate gyrus; disease course; glia; hippocampus; immunofluorescence; immunohistochemistry; immunoreactivity; in vitro study; internalization; light chain; macroglia; microglia; mouse; neuropathology; nonhuman; priority journal; protein degradation; protein processing; rat; senescence; stratum radiatum; transgenic mouse; Alzheimer disease; animal; autophagy; C57BL mouse; cell culture; disease model; glia; metabolism; pathology; physiology; tumor cell line; Alzheimer Disease; Amyloid beta-Peptides; Animals; Autophagy; Cell Line, Tumor; Cells, Cultured; Dentate Gyrus; Disease Models, Animal; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroglia; Rats
Año:2016
Volumen:26
Número:2
Página de inicio:194
Página de fin:210
DOI: http://dx.doi.org/10.1002/hipo.22503
Título revista:Hippocampus
Título revista abreviado:Hippocampus
ISSN:10509631
CODEN:HIPPE
CAS:amyloid beta protein, 109770-29-8; congo red, 573-58-0, 80701-77-5; ubiquitin, 60267-61-0; Amyloid beta-Peptides
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10509631_v26_n2_p194_Pomilio

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Citas:

---------- APA ----------
Pomilio, C., Pavia, P., Gorojod, R.M., Vinuesa, A., Alaimo, A., Galvan, V., Kotler, M.L.,..., Saravia, F. (2016) . Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization. Hippocampus, 26(2), 194-210.
http://dx.doi.org/10.1002/hipo.22503
---------- CHICAGO ----------
Pomilio, C., Pavia, P., Gorojod, R.M., Vinuesa, A., Alaimo, A., Galvan, V., et al. "Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization" . Hippocampus 26, no. 2 (2016) : 194-210.
http://dx.doi.org/10.1002/hipo.22503
---------- MLA ----------
Pomilio, C., Pavia, P., Gorojod, R.M., Vinuesa, A., Alaimo, A., Galvan, V., et al. "Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization" . Hippocampus, vol. 26, no. 2, 2016, pp. 194-210.
http://dx.doi.org/10.1002/hipo.22503
---------- VANCOUVER ----------
Pomilio, C., Pavia, P., Gorojod, R.M., Vinuesa, A., Alaimo, A., Galvan, V., et al. Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization. Hippocampus. 2016;26(2):194-210.
http://dx.doi.org/10.1002/hipo.22503