title: Multimodal analysis in acute and chronic experimental autoimmune encephalomyelitis.
abstract: Different experimental autoimmune encephalomyelitis models (EAE) have been developed. However, due to the different experimental conditions applied, observations simultaneously considering different pathological targets are still scarce. Using EAE induced in Dark Agouti rats with syngenic whole spinal cord homogenate suspended in incomplete Freund's adjuvant, we here analyze neurosteroidogenic machinery, cytokine levels, microglial cells, infiltration of inflammatory cells, myelin proteins and Na(+), K(+)-ATPase pump activity in the spinal cord. Data obtained in the acute phase of the disease confirmed that neurological signs were accompanied by the presence of perivascular infiltrating T cells (CD3(+) cells) and activated monocytic/microglial cells (ED1(+) and MHC-II(+)) in the spinal cord. In particular, the number of MHC-II(+) cells was significantly increased in association with increased expression of pro- (i.e., TNF-α, IL-1β) and anti-inflammatory (i.e., TGF-β) cytokines as well as with decreased expression of proteolipid protein and myelin basic protein. During the chronic phase of the disease, the number of MHC-II(+) cells was still increased, although less than in the acute phase. Changes in the number of MHC-II(+) cells were associated with decreased Na(+),K(+)-ATPase enzymatic activity. A general decrease in the levels of neuroactive steroids, with the exception of an increase in tetrahydroprogesterone and 17β-estradiol, was detected in the acute phase. These changes were maintained or reverted in the chronic phase of EAE. In conclusion, we report that modifications in the neuroimmune response in the acute and chronic phases of EAE are associated with specific changes in myelin proteins, Na(+),K(+)-ATPase pump and in the levels of neuroactive steroids.
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari-Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giatti
authors.forename: Mariaserena
authors.initials: M
authors.lastname: Boraso
authors.forename: Federico
authors.initials: F
authors.lastname: Abbiati
authors.forename: Elisa
authors.initials: E
authors.lastname: Ballarini
authors.forename: Donato
authors.initials: D
authors.lastname: Calabrese
authors.forename: Maria
authors.initials: M
authors.lastname: Santos-Galindo
authors.forename: Roberta
authors.initials: R
authors.lastname: Rigolio
authors.forename: Marzia
authors.initials: M
authors.lastname: Pesaresi
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.forename: Barbara
authors.initials: B
authors.lastname: Viviani
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Roberto Cosimo
authors.initials: RC
authors.lastname: Melcangi
mesh_terms: D000208:Acute Disease; D000818:Animals; D001772:Blood Cell Count; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D005470:Fluorometry; D005802:Genes, MHC Class II / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D009185:Myelin Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000473:pathology; D020556:Neutrophil Infiltration / Q000502:physiology; D023282:Nuclease Protection Assays; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D009185:Myelin Proteins; D013256:Steroids; D012260:Ribonucleases; D000254:Sodium-Potassium-Exchanging ATPase