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PhD ceremony Mr. V. Kannan: Modulation of microglial activity

When:Mo 01-07-2013 at 14:30

PhD ceremony: Mr. V. Kannan, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Modulation of microglial activity

Promotor(s): prof. H.W.G.M. Boddeke

Faculty: Medical Sciences

Microglia are the primary immune cells of the central nervous system. Microglia are important for neuronal support, tissue homeostasis, antigen presentation and removal of apoptotic cells. Normally, microglia are highly ramified and are responsible for immune surveillance. Under pathological conditions, microglia can become activated and transform to an amoeboid shape with an increased expression of surface markers and release of inflammatory cytokines for repair and tissue regeneration. Excessive microglia activation is associated with neurodegenerative conditions and ageing.

Therefore, it is important to identify factors that can modulate microglia inflammatory responses. Here, histone deacetylases (HDACs) were studied as factors modulating inflammatory responses in primary microglia and in experimental autoimmune encephalomyelitis, a demyelinating disorder. Microglia express a variety of receptors to monitor their surroundings, including purinergic and chemokine receptors. Purinergic receptors are important sensors of neuronal stress and the purinergic P2X7 receptor is involved in neuronal protection. The neuroprotective effect of the P2X7 receptor, and the effect of HDAC inhibitors on P2X7 expression by microglia was investigated in hippocampal slice cultures. Chemokine receptors and chemokines are important for the regulation of microglia migration. Inhibition of CXCR3-mediated microglia chemotaxis by chemokine-like receptor CCX-CKR was determined.

Summarizing, the data presented in this thesis show that HDACs have an important role in the glial inflammatory response and are possibly important targets in demyelinating disorders. Purinergic and chemokine receptors were demonstrated to have an important role in the regulation of inflammatory responses in microglia and other immune cells.

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