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Identifier

000448002

Title

The role of aconitate decarboxylase 1 in neuroinflammation

Alternative Title

Ο ρόλος της αποκαρβοξυλάσης του ακονικού οξέος 1 στην νευροφλεγμονή

Author

Καραδήμα, Ελευθερία

Thesis advisor

Αλεξάκη, Βασιλεία Ισμήνη

Reviewer

Χαραλαμπόπουλος, Ιωάννης
Βεργίνης, Παναγιώτης

Abstract

Microglia are resident immune cells of the central nervous system which are implicated in neurogenesis and synaptic pruning. They are characterized by a homeostatic phenotype surveilling the brain parenchyma, but in several neurodegenerative and neuroinflammatory diseases their phenotype is shifted to a disease-associated state. Aconitate decarboxylase 1 (ACOD1), which is encoded by the Irg1 gene, is an enzyme that catalyzes the production of itaconate from cis-aconitate, a TCA cycle intermediate. Extensive research in macrophages has demonstrated the anti-inflammatory effects of the metabolite itaconate. Aim of the present study was to delineate the potential role of itaconate in microglia cells by the use of the mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Irg1-/- mice subjected to EAE presented milder progression of the disease, however reached similar clinical scores compared to wild-type littermates at day 15 post-immunization. T cell and myeloid (microglia, monocyte, dendritic) cell infiltration was not different in spinal cords of wild-type and Irg1-/- EAE mice. Itaconate levels and Irg1 mRNA levels were elevated in spinal cords of wild-type but not Irg1-/- EAE mice in comparison to healthy mice. Moreover, citrulline levels were increased in the spinal cords of Irg1-/- compared to wild-type EAE mice, suggesting changes in arginine metabolism in absence of itaconate. In conclusion, ACOD1 deficiency results in milder EAE progression and changes in arginine metabolism. Further studies are required to delineate the underlying mechanisms.

Language

English

Subject

Itaconate

Microglia

Ιτακονικό οξύ

Μικρόγλοια

Issue date

2022-03-30

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses

Type of Work--Post-graduate theses