Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis

BMC Neuroscience

Research Article

Giulia D'Intino¹  Sandra Sivilia¹  Alessandro Massella¹  Luca Lorenzini¹  Roberto C Melcangi²  Silvia Giatti²  Mercedes Fernández³  Luciana Giardino⁴  Laura Calzà⁴ 

[1] Department of Veterinary Medicine, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, Italy;Dept. of Endocrinology, Pathophysiology and Applied Biology - Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milano, Italy;Health Sciences and Technology - Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, Italy;Health Sciences and Technology - Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, Italy;Department of Veterinary Medicine, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, Italy;

关键词: experimental allergic encephalomyelitis;    gender-related;    rat;    spinal cord;    cerebellum;    neurotrophins and related receptors;   

DOI  :  10.1186/1471-2202-13-12

 received in 2011-08-25, accepted in 2012-01-24,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMultiple 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.Results1. 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.ConclusionsIt 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.

【 授权许可】

Unknown   
© Massella et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.