THE RECOVERY EFFECT OF STEM CELLS AND KAMPO MEDICINE KAMIKIHITO ON SOCIAL BEHAVIOR DYSFUNCTIONS IN REFRACTORY PSYCHIATRIC DISORDERS

Abstract Background The brain pathophysiology of social dysfunctions in depression and autism spectrum disorder are complex, and there is a growing need to understand the relevant neuronal circuit alterations and to find direct and effective treatments for their recoveries. Aims & Objectives In this study, we have investigated the influences of bone marrow-derived mesenchymal stem cell (MSC) transplantation and Japanese Kampo medicine, Kamikihito on social behaviors as a novel treatment options for intractable psychiatric disorders, using refractory depression animal model related to stress vulnerability, we had preliminary established, induced by dual stress during embryonic/juvenile period (Furuse et al., 2019). Method We explored the possibility that MSC transplantation, which we have demonstrated the recovery effect on behavioral abnormalities in refractory depression model (Kigawa et al., 2014), and Kamikihito that has been used for anxiety and nervousness in clinics and recently reported to induce changes in emotional and social functions via oxytocinergic neuron enhancement (Tsukada et al., 2021), may promote neural repair and regeneration in brain regions related to social cognition and empathy, which in turn may enhance recovery for social dysfunctions. Results In the refractory depression model, active social interaction behavior, as indicated in the social interaction test, was reduced by approximately 50%. In contrast, treatments of MSC alone or MSC and kamikihito significantly improved social interaction behavior, which was reduced in the model animal. On the other hand, no such effects were observed in the group treated with kamikihito alone. In the model group, contact time with the restrained individual and empathy-like voluntary behavior as indicated by rescue behavior were reduced by approximately 40%. Interestingly, the reduction of empathy-like behavior in the model group was significantly improved in the groups treated with kamikihito alone and in the group treated with kamikihito and MSC. On the other hand, MSC monotreatment group could not show any effect. Discussion & Conclusion We would add some data of analyzing changes of dynamics of oxytocinergic neurons from the hypothalamic paraventricular nucleus, Parvalbumin (PV)/somatostatin (SS) positive GABA interneuron changes in brain regions including the cingulate cortex, amygdala, and hippocampus in each animal group, and identify brain circuit mutations that lead to social cognitive behavioral abnormalities for revealing the mechanisms of their recoveries.