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Projekt
Role of the cannabinoid receptor 2 (CB2) in neuroinflammation
Antragstellerin
Professorin Dr. Judith Alferink
Fachliche Zuordnung
Biologische Psychiatrie
Förderung
Förderung von 2011 bis 2016
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 42860621
Our previous work demonstrated the impact of the cannabinoid receptor 2 (CB2) in the control of IFN- γ responses and microglial activation during neuroinflammation in chronic pain. Since both immune processes are known to influence the pathogenesis of parasite-induced encephalitis, we also investigated CB2 signaling in cerebral malaria (CM) and Toxoplasma gondii encephalitis (TE). Plasmodium berghei ANKA (PbA)-infected CB2 knockout (Cnr2-/-) mice exhibit enhanced survival, while all wild type (WT) controls succumb to disease. A reduced blood vessel sequestration and an intact blood brain barrier identified in infected Cnr2-/- mice could cause increased resistance. In addition, diminished neuroinflammatory responses occur in Cnr2-/- animals with reduced numbers of CNS-immigrated CD8 T cells and activated myeloid cells. Importantly, therapeutic application of the CB2 antagonist SR122458 confers enhanced CM resistance in C57BL/6 mice. A functional role of CB2 in the immunopathogenesis of TE was further demonstrated in T. gondii-infected Cnr2-/- mice which exhibit enhanced mortality. Here we plan to investigate the underlying CB2-mediated immune mechanisms in parasite encephalitis by assessing Cnr2-/- and bone-marrow-chimeric mice and CB2- based pharmacological approaches. To dissect the specific roles of CB2 signaling in lymphocytes and/or myeloid cells during neuroinflammation, cell-specific CB2 conditional knockout mice will be investigated. We aim to define novel CB2-dependent mechanisms with therapeutic potential involved in the control of neuroinflammatory responses.
DFG-Verfahren
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