Neuronal ICAM-5 regulates synaptic maturation and microglia functions

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Title: Neuronal ICAM-5 regulates synaptic maturation and microglia functions
Author: Paetau, Sonja
Contributor: University of Helsinki, Faculty of Biological and Environmental Sciences
Doctoral Programme Brain and Mind
Thesis level: Doctoral dissertation (article-based)
Belongs to series: URN:ISSN:2342-317X
Abstract: The human brain continues to fascinate generation after generation of neuroscientists. Our knowledge is expanding at an accelerating rate, yet the details of memory formation and information processing remain an enigma. The purpose of this work has been to provide novel insights into how the brain operates on a molecular level, with the focus on one particular protein, the intercellular adhesion molecule (ICAM)-5. The human brain is more than just the sum of its components. It is fundamental that the different cell types that reside in the brain work together in perfect harmony, each playing their own role, still in tune with each other. In this dissertation I have investigated the ICAM-5 mediated communication between neurons and the resident immune cells of the brain, the microglia. First, we identified a molecular mechanism, by which ICAM-5 plays a role as a negative regulator of spine maturation. In the young spine, ICAM-5 competes with glutamate receptors for binding to the cytoskeletal anchor �-actinin. Synaptic transmission induces a cleavage of the extracellular ICAM-5, and the maturation process of the spine is allowed to proceed. Next, we showed that the consequentially solubilized fragment of ICAM-5 is bound by microglia and affects them. Soluble ICAM-5 inhibits phagocytosis and promotes an anti-inflammatory phenotype in immune challenged microglia. Taken together, these results suggest that ICAM-5 is a versatile molecule that plays a role in synaptic maturation and immunology. It is tempting to speculate on a role for ICAM-5 in synaptic pruning, however this line of research remains in the future scope for now.Hjärnan är ett komplext organ som är väl isolerat från resten av kroppen. Den består av nervceller som processerar information, samt stödceller. En av dessa stödceller kallas mikroglia och de sköter immunförsvaret i hjärnan. Det har visat sig att dessa celler även påverkar hur nervcellerna kommunicerar med varandra, hur de mognar och utvecklas. I min avhandling har jag forskat i hur ett protein från nervcellerna påverkar synapsmognaden och immunfunktioner i hjärnan. Det visade sig att nervceller kan klyva detta protein som då binds av mikroglia och gör dem mindre inflammatoriska. Då ICAM-5 klyvs til följd av robust kommunikation mellan två nervceller, så lossnar den intracellulära delen av ICAM-5 från cellen skelett och detta tillåter synapsen att mogna. ICAM-5 är således en mycket intressant molekyl i hjärnan som påverkar både hur minnet formas och hur immunförsvaret fungerar.
URI: URN:ISBN:978-951-51-4267-2
Date: 2018-06-29
Rights: This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.

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