CB2 cannabinoid receptor impact on dopamine neuron and microglia cross-talk

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講演要旨

Advances in molecular biology techniques including genetic tools have provided new knowledge and deeper insights in understanding the biological roles of the endocannabinoid system in psychiatric disorders. The remarkable advances in genetics of endocannabinoid system (ECS) are unravelling the genetic bases in a number of neuropsychiatric disorders, including depression, schizophrenia, addiction, autism spectrum disorders and neurological conditions of neuro-immune disorders. The ECS consists of two major receptors (CB1Rs and CB2Rs), endocannabinoids (eCBs) and the synthesizing and degradation enzymes for eCBs. Although CB1Rs have been well characterized, the neuronal expression of CB2Rs and their role in neuropsychiatric have been subjects of long standing controversy and debate despite new knowledge and advances. The new molecular techniques and transgenic approaches are being used to explore and identify the involvement of the elements of ECS in models of CNS function and dysfunction underlying neuropsychiatric disorders. There is also increasing global awareness and interest in cannabis and cannabinoid therapeutics. In this seminar presentation, data from our studies with a background on dysfunction of ECS genes in neuropsychiatric disorders, and the methods and approaches that were used to assess the neurobehavioral and molecular changes associated with the functions of specific genes. Association studies were performed between polymorphisms in CNR2 gene and neuropsychiatric disorders in two independent case-control populations. We identified novel human and rodent CB2R isoforms with differential tissue expression patterns and regulation by CBR ligands. We report that there is association between polymorphisms of CNR2 gene and psychosis, eating disorders, depression and alcoholics in the human populations investigated. Neuroimmune signaling and neuroinflammation is emerging as a key component in the effects of CB2Rs that are expressed in macrophages, microglia, and neurons and are regulators of the immune response. Thus, there is compelling evidence from our studies and current knowledge from mice to human subjects that manipulations of the components of the ECS may be useful in psychiatric disorders.