| Egr1 expression is induced following glatiramer acetate immunotherapy in rodent models of glaucoma and Alzheimer's disease. | |
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MedLine Citation:
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PMID: 21969301 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Immunization with glatiramer acetate (GA) alleviates the neuropathology associated with glaucoma and Alzheimer's disease (AD) in rodent models. This research was undertaken to screen for molecular factors underlying GA-induced neuroprotective mechanisms in these models of chronic neurodegeneration. METHODS: Gene expression profiles were analyzed in GA-immunized versus nonimmunized elevated-intraocular pressure (IOP) rat models of glaucoma by using whole genome cDNA microarrays and were further validated by quantitative real-time PCR analysis. A gene, prominently upregulated by GA in elevated IOP retina, was further studied in APP(SWE)/PS1(ΔE9)-transgenic (AD-Tg) mice after GA immunization. RESULTS: Seven days after treatment with GA, numerous genes were regulated in the retinas of rats with elevated IOP. Comprehensive functional classification and DAVID/KEGG enrichment analysis of GA-induced differentially expressed genes revealed annotation terms and pathways involved in neuroprotection, immune responses, cell communication, and regeneration. Specifically, increased mRNA levels of an early growth response (Egr) 1 gene were evident in GA-immunized retinas with elevated IOP. In AD-Tg mice, a significant increase in hippocampal EGR1 protein levels was also found in response to GA immunization. Nuclear EGR1 in the dentate gyrus colocalized more frequently with doublecortin-positive and Ki67 proliferating neural progenitors in GA-immunized as compared to nonimmunized AD-Tg mice. Further, EGR1 levels were negatively correlated with hippocampal amyloid-β plaque burden. CONCLUSIONS: This study presents global gene expression profiles associated with GA immunization in a glaucoma rat model. Moreover, it identifies EGR1 transcription factor as a potential mediator for GA-induced neuroprotection in both glaucoma and AD. |
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Authors:
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Sharon Bakalash; Michael Pham; Yosef Koronyo; Brenda C Salumbides; Andrei Kramerov; Hillary Seidenberg; Dror Berel; Keith L Black; Maya Koronyo-Hamaoui |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-11-21 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 52 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: 2012-01-16 Revised Date: 2013-01-09 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 9033-46 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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drug therapy*,
genetics,
immunology Animals Chronic Disease Disease Models, Animal Early Growth Response Protein 1 / genetics* Female Gene Expression / drug effects, immunology Glaucoma / drug therapy*, genetics, immunology Hippocampus / physiology Immunosuppressive Agents / pharmacology* Male Mice Mice, Transgenic Nerve Degeneration / drug therapy, genetics, immunology Neuroprotective Agents / pharmacology Oligonucleotide Array Sequence Analysis Peptides / pharmacology* Rats Rats, Inbred Lew Real-Time Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Early Growth Response Protein 1; 0/Egr1 protein, mouse; 0/Egr1 protein, rat; 0/Immunosuppressive Agents; 0/Neuroprotective Agents; 0/Peptides; 0/copolymer 1 |
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