Validation experiment designed to validate causal mechanisms targeting CNR2 in C57BL/6 mice with B10.BR donor transplants. Primary outcome: behavioral changes including immobility and struggling behaviors
This study examined whether genetic deletion of the type 2 cannabinoid receptor (CB2R) could rescue acute behavioral dysregulation produced by graft versus host disease (GVHD) in mice. GVHD was induced by irradiation followed by infusion of bone marrow and splenocytes from major histocompatibility complex-mismatched donors. The researchers compared behavioral outcomes between wild-type mice, global CB2R knockout mice, and mice with CB2R deletion specifically in CX3CR1-expressing cells (including microglia). A comprehensive battery of behavioral tests was performed 14-18 days after transplant to assess various aspects of behavior including locomotor activity, depression-like behavior, social interactions, anhedonia, motor coordination, and anxiety-like behavior.
GVHD induction by irradiation followed by BM and splenocyte infusion from MHC-mismatched B10.BR donors into C57BL/6 recipients. Behavioral testing battery performed 14-18 days post-transplant including open field, forced swim, social interaction, sucrose consumption, rotarod, and anxiety tests.
Expected that CB2R deletion would protect against GVHD-induced behavioral dysregulation based on previous findings showing protection against neuroinflammation and neuronal loss
Rescue of GVHD-induced behavioral abnormalities in CB2R knockout mice compared to wild-type mice
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