The role of infected and activated microglia in the pathogenesis of psychiatric disorders

• Antragstellerin: Dr. Daniela Krause
• Fachliche Zuordnung: Biologische Psychiatrie
• Förderung: Förderung von 2009 bis 2010
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 150591430

The precise pathophysiology of schizophrenia still remains unclear. It has been suggested that a loss of gray matter and cerebral volume is associated with neurodegenerative processes. One explanation for the possible underlying neuronal damage might the activation of microglia, as activated microglia can be neurotoxic. Microglia, immunogenic brain cells, get activated via contact with infectious agents. Increasing evidence indicates that infectious agents are important in the pathogenesis of psychiatric disorders. The precise mechanisms, whether infections cause brain lesions or influence the immune balance to contribute to mental diseases, is still controversial. A route could be an activation of the tryptophan catabolism, located in microglia. Tryptophan is an essential amino acid that functions as a precursor for neurotransmitters like serotonin and becomes degraded by the kynurenine pathway. The products of this catabolism can modulate the neurotransmitter balance. In psychiatric diseases, dysregulations in various neurotransmitter systems are responsible for their occurrence. A possible hypothesis could be that cerebral bacterial and viral exposure results in activated microglia, which subsequently influence the neurotransmitter balance via the tryptophan pathway. For this hypothesis, human microglia can be investigated in cell cultures and activated via infections; then the tryptophan metabolism needs to be measured. A deeper insight into the precise mechanism of how infections influence the immune system, tryptophan metabolism and the resulting neurotransmitter availability could help finding new therapeutic strategies for psychiatric diseases.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeberin: Professorin Sunhee C. Lee