title: Egr1 expression is induced following glatiramer acetate immunotherapy in rodent models of glaucoma and Alzheimer's disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Bakalash
authors.forename: Michael
authors.initials: M
authors.lastname: Pham
authors.forename: Yosef
authors.initials: Y
authors.lastname: Koronyo
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Salumbides
authors.forename: Andrei
authors.initials: A
authors.lastname: Kramerov
authors.forename: Hillary
authors.initials: H
authors.lastname: Seidenberg
authors.forename: Dror
authors.initials: D
authors.lastname: Berel
authors.forename: Keith L
authors.initials: KL
authors.lastname: Black
authors.forename: Maya
authors.initials: M
authors.lastname: Koronyo-Hamaoui
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D000068717:Glatiramer Acetate; D005901:Glaucoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006624:Hippocampus / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C486110:Egr1 protein, rat; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D010455:Peptides; D000068717:Glatiramer Acetate