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Adult and neonatal astrocytes exhibit diverse gene expression profiles in response to beta amyloid ex vivo
Antti Kurronen1,2; Rea Pihlaja1,2; Eveliina Pollari1,2; Katja Kanninen1,2; Markus Storvik3; Garry Wong1,2,4; Milla Koistinaho2,5; Jari Koistinaho1,2,6
2012-05
Source PublicationWorld Journal of Neuroscience
ISSN2162-2000
Volume2Issue:2Pages:57-67
Abstract

Astrocytes are implicated in the neuropathology of Alzheimer’s disease (AD) by clustering with other activated inflammatory cells at the sites of amyloid beta (Aβ) deposits formed in the cortex and hippocampus. Astrocytes are known to contribute to the clearance of Aβ in the AD brain. Also, adult but not neonatal mouse astrocytes are able to clear Aβ deposits from the tissue sections of transgenic AD mice and human brain ex vivo. Because these findings suggest that cultured neonatal astrocytes may not represent a relevant cell for modeling the function of astrocytes in neurodegenerative diseases, we studied whether neonatal and adult astrocytes show different responses in gene expression when exposed to brain sections burdened by deposits of human Aβ. Whole genome microbarrays demonstrated greater alteration of gene expression in adult astrocytes than in neonatal astrocytes. When exposed to Aβ burdened brain sections adult but not neonatal astrocytes up-regulated genes related to peptidase (such as MMP13, MMP12, Phex, Htra1), scavenger receptor (Scara5, Enpp2) and glutathioine transferase (Gsta1, Gsta2, Gclm) activity, suggesting increased ability to degrade and endocytose Aβ peptides and protect against oxidative bursts. Quantitative RT-PCR analysis confirmed the significant alteration in gene expression of key peptidases, scavenger receptors and cholesterol synthesis. Our data suggest that adult astrocytes in culture are more sensitive to disease-relevant stress showing more extensive genetic response compared to neonatal astrocytes. In addition, the identified peptidases and scavenger receptors which increase expression selectively in adult astrocytes suggest their major role in astrocyte-mediated clearance of Aβ deposits in AD.

KeywordAlzheimer’s Disease Astrocytes Mice Amyloid Beta Gene Expression Microarray Analysis Endocytosis Proteolysis
DOIhttp//doi.org/10.4236/wjns.2012.22009
Language英语
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Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorJari Koistinaho
Affiliation1.Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
2.Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
3.School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
4.Department of Biosciences, University of Eastern Finland, Kuopio, Finland
5.Medeia Therapeutics Ltd., Kuopio, Finland
6.Department of Oncology, Kuopio University Hospital, Kuopio, Finland
Recommended Citation
GB/T 7714
Antti Kurronen,Rea Pihlaja,Eveliina Pollari,et al. Adult and neonatal astrocytes exhibit diverse gene expression profiles in response to beta amyloid ex vivo[J]. World Journal of Neuroscience,2012,2(2):57-67.
APA Antti Kurronen.,Rea Pihlaja.,Eveliina Pollari.,Katja Kanninen.,Markus Storvik.,...&Jari Koistinaho.(2012).Adult and neonatal astrocytes exhibit diverse gene expression profiles in response to beta amyloid ex vivo.World Journal of Neuroscience,2(2),57-67.
MLA Antti Kurronen,et al."Adult and neonatal astrocytes exhibit diverse gene expression profiles in response to beta amyloid ex vivo".World Journal of Neuroscience 2.2(2012):57-67.
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