Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization

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 a...

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Autores principales:	Alaimo, Agustina, Kotler, Mónica Lidia
Publicado:	2016
Materias:	AD Astrocytes Hilus LC3 Microglia Neuroinflammation Stratum radiatum Ubiquitin amyloid beta protein cell protein congo red Iba1 protein protein p62 ubiquitin unclassified drug 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 animal C57BL mouse cell culture disease model 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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10509631_v26_n2_p194_Pomilio http://hdl.handle.net/20.500.12110/paper_10509631_v26_n2_p194_Pomilio
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_10509631_v26_n2_p194_Pomilio
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spelling	paper:paper_10509631_v26_n2_p194_Pomilio2023-06-08T16:02:56Z Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization Alaimo, Agustina Kotler, Mónica Lidia 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 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. Fil:Alaimo, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kotler, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10509631_v26_n2_p194_Pomilio http://hdl.handle.net/20.500.12110/paper_10509631_v26_n2_p194_Pomilio
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Alaimo, Agustina Kotler, Mónica Lidia Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization
topic_facet	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
description	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.
author	Alaimo, Agustina Kotler, Mónica Lidia
author_facet	Alaimo, Agustina Kotler, Mónica Lidia
author_sort	Alaimo, Agustina
title	Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization
title_short	Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization
title_full	Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization
title_fullStr	Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization
title_full_unstemmed	Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization
title_sort	glial alterations from early to late stages in a model of alzheimer's disease: evidence of autophagy involvement in aβ internalization
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10509631_v26_n2_p194_Pomilio http://hdl.handle.net/20.500.12110/paper_10509631_v26_n2_p194_Pomilio
work_keys_str_mv	AT alaimoagustina glialalterationsfromearlytolatestagesinamodelofalzheimersdiseaseevidenceofautophagyinvolvementinabinternalization AT kotlermonicalidia glialalterationsfromearlytolatestagesinamodelofalzheimersdiseaseevidenceofautophagyinvolvementinabinternalization
_version_	1768543336697692160

Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization

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