title: Efficacy of the selective progesterone receptor agonist Nestorone for chronic experimental autoimmune encephalomyelitis.
abstract: Progesterone plays a protective role in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Besides spinal cord neuropathology, MS patients present a dysfunctional hippocampus. In this work we studied the therapeutic effects of the progestin Nestorone in the brain of mice with chronic EAE. Nestorone decreased clinical grade and enhanced motor behavior. In addition, it increased cell proliferation and doublecortin positive neuroblasts in the hippocampus, increased GABAergic interneurons and attenuated the number of Iba1+ microglia/macrophages, events possibly linked to enhancement of neurogenesis. Therefore, Nestorone protected against hippocampus abnormalities and improved functional outcomes of EAE mice, suggesting its potential value for MS.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Dept. of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Garay
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Dept. of Physiology, Faculty of Medicine, University of Buenos Aires, Argentina.
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Gonzalez Deniselle
authors.affiliation: Population Council, Rockefeller University, New York, USA.
authors.forename: Regine
authors.initials: R
authors.lastname: Sitruk-Ware
authors.affiliation: UMR 788 Inserm, University Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: Rachida
authors.initials: R
authors.lastname: Guennoun
authors.affiliation: UMR 788 Inserm, University Paris-Sud, Kremlin-Bicêtre, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Schumacher
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina; Dept. of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Argentina. Electronic address: alejandrodenicola@gmail.com.
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002908:Chronic Disease; D000089622:Doublecortin Domain Proteins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009479:Neuropeptides / Q000378:metabolism; D009653:Norprogesterones / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity; D010751:Phosphopyruvate Hydratase / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; C499047:Mbp protein, mouse; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009479:Neuropeptides; D009653:Norprogesterones; D010446:Peptide Fragments; C029167:ST 1435; D005620:Freund's Adjuvant; D010751:Phosphopyruvate Hydratase
keywords: Behavior; Experimental autoimmune encephalomyelitis; Microglia; Nestorone