title: Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) varies considerably in its incidence and progression in females and males. In spite of clinical evidence, relatively few studies have explored molecular mechanisms possibly involved in gender-related differences. The present study describes possible cellular- and molecular-involved markers which are differentially regulated in male and female rats and result in gender-dependent EAE evolution and progression. Attention was focused on markers of myelination (MBP and PDGFαR) and neuronal distress and/or damage (GABA synthesis enzymes, GAD65 and GAD67, NGF, BDNF and related receptors), in two CNS areas, i.e. spinal cord and cerebellum, which are respectively severely and mildly affected by inflammation and demyelination. Tissues were sampled during acute, relapse/remission and chronic phases and results were analysed by two-way ANOVA.
  
  
  RESULTS
  1. A strong gender-dependent difference in myelin (MBP) and myelin precursor (PDGFαR) marker mRNA expression levels is observed in control animals in the spinal cord, but not in the cerebellum. This is the only gender-dependent difference in the expression level of the indicated markers in healthy animals; 2. both PDGFαR and MBP mRNAs in the spinal cord and MBP in the cerebellum are down-regulated during EAE in gender-dependent manner; 3. in the cerebellum, the expression profile of neuron-associated markers (GAD65, GAD67) is characterized by a substantial down-regulation during the inflammatory phase of the disease, which does not differ between male and female rats (two-way ANOVA); 4. there is an up-regulation of NGF, trkA and p75 mRNA expression in the early phases of the disease (14 and 21 days post-immunization), which is not different between male and female.
  
  
  CONCLUSIONS
  It is reported herein that the regulation of markers involved in demyelination and neuroprotection processes occurring during EAE, a well-established MS animal model, is gender- and time-dependent. These findings might contribute to gender- and phase disease-based therapy strategies.
authors.affiliation: Department of Veterinary Medicine, University of Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Massella
authors.forename: Giulia
authors.initials: G
authors.lastname: D'Intino
authors.forename: Mercedes
authors.initials: M
authors.lastname: Fernández
authors.forename: Sandra
authors.initials: S
authors.lastname: Sivilia
authors.forename: Luca
authors.initials: L
authors.lastname: Lorenzini
authors.forename: Silvia
authors.initials: S
authors.lastname: Giatti
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Melcangi
authors.forename: Laura
authors.initials: L
authors.lastname: Calzà
authors.forename: Luciana
authors.initials: L
authors.lastname: Giardino
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism*; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; C010491:neurotropin; D005620:Freund's Adjuvant; D020796:Receptor, Platelet-Derived Growth Factor alpha; D005968:Glutamate Decarboxylase