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

DOI: 10.1186/1471-2202-13-12

Keywords: experimental allergic encephalomyelitis, gender-related, rat, spinal cord, cerebellum, neurotrophins and related receptors

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Abstract:

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.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.Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), which can progress over decades. The progressive failure of remyelination leads to the cumulative loss of axons, grey matter atrophy and prevalent neurodegeneration responsible for chronic disability and cognitive decline [1]. There is a considerable difference in the way MS affects females and males, as has been highlighted by epidemiology studies and MRI analyses [2-4]. The way of gender-influence in MS is complex and still obscure. From a pathogenic point of view, females tend to have stronger Th1-mediated immune responses and are more prone to develop autoimmune diseases, including MS [5]. However, gender might influence white matter establishment and maintenance of the mature structure of white tracts, thus affecting their

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