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Theses

Identification de programmes d'activation macrophagique et microgliale dans les formes progressives de la sclérose en plaques

Abstract : Multiple sclerosis (MS) is a chronic neuro-inflammatory disease and the most common cause of chronic neurological disability in young adults. No treatment is currently available to prevent the aggravation of symptoms in the progressive forms of the disease. The involvement of macrophages and microglia in demyelination and axonal injury is well known but need to be further characterized. Especially, the high level of functional plasticity harboured by macrophages/ microglia suggests that these cells engage specific activation programs depending on the disease, its evolution stage and the localization of lesions. In this context, this phD thesis was essentially aimed to characterize macrophage/microglia activation programs in two categories of tissue alterations observed in the post-mortem central nervous system from MS patients: 1) partially demyelinated areas at the border of spinal cord plaques and 2) cortical lesions. These two particular types of lesions are both highly frequent in progressive forms of MS and suspected to be involved in chronic and irreversible neurological disability. Using an in silico approach, the macrophage/microglia activation programs identified in MS were then compared to those observed in neurodegenerative and inflammatory disorders such as Alzheimer's disease and Parkinson's disease. Overall, our results suggest that the chronic activation of macrophages and microglia largely contributes to the slow and chronic expansion of MS lesions in progressive forms of the disease. Our work also proposes new therapeutic targets
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https://tel.archives-ouvertes.fr/tel-01056829
Contributor : Abes Star :  Contact
Submitted on : Wednesday, August 20, 2014 - 3:22:11 PM
Last modification on : Wednesday, November 20, 2019 - 3:01:35 AM
Long-term archiving on: : Thursday, November 27, 2014 - 12:05:47 PM

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  • HAL Id : tel-01056829, version 1

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Alice Lhuillier. Identification de programmes d'activation macrophagique et microgliale dans les formes progressives de la sclérose en plaques. Neurosciences [q-bio.NC]. Université Claude Bernard - Lyon I, 2014. Français. ⟨NNT : 2014LYO10096⟩. ⟨tel-01056829⟩

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