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Tesi etd-05122017-001416

Thesis type
Tesi di laurea magistrale
Physiology of Oligodendrocyte Precursor Cells (OPCs) and Methylthioadenosine (MTA) treatment to potentiate endogenous remyelination in Multiple Sclerosis
Corso di studi
relatore Prof. Casini, Giovanni
Parole chiave
  • remyelination
  • OPC
  • multiple scelerosis
  • methylthioadenosine
Data inizio appello
Data di rilascio
Riassunto analitico
Multiple Sclerosis (MS) is an autoimmune demyelinating disease of central nervous system (CNS) with neurodegenerative aspects and inflammatory response. The extent of this disease is a major health issue since it is affecting over two million people in the world. In MS there is an initial spontaneous remyelination from Oligodendrocyte precursor Cells (OPCs), present in the adult CNS up to 9% of the total cells. Proliferating OPCs are recruited to MS lesions but differentiation into myelinating Oligodendrocyte (OL) is compromised and leads to failure of remyelination and functional deficiency.
The induction of OPCs differentiation is a critical event to understand as the prerequisite for successful myelination. The therapies currently used in clinics to treat MS are immunemodulators focusing on reducing the inflammatory process and, subsequently, to reduce the number and intensity of clinical relapses. To date, there are no effective remyelination therapies and the first proposed neuroprotectors are still under clinical trials.
The aim of this project was to study the physiological properties of OPCs in vitro and how to potentiate endogenous remyelinating capacities with pharmacological agents.
The experiments were performed with primary mixt glial cell culture obtained from the cerebral cortex of P7 CD1 mice. After 7-10 days of glial culture, OPCs were isolated by shake-off method. Methylthioadenosine (MTA) drug was tested at different concentration in isolated OPCs. This pharmacological treatment has been shown to promote OPC proliferation in animal models of MS. Immunocytochemical techniques were performed in order to study survival and proliferation of OPCs in vitro. Markers were detected by fluorescence microscopy. Images obtained were analysed through ImageJ software and results submitted to statistical analysis.
Studies on pharmacology agents and a better understanding of OPCs physiology might be an opportunity to study potential remyelination and therefore to avoid the neurodegenerative phase of MS and other demyelinating diseases. These pro-myelinating therapies are a real challenge for current Neurology.