[Potential therapy of intravenous neural stem cell transplantation for psychiatric disorder--a strategy for facilitation of neural network and behavioral recovery].

Abstract

Recent clinical neuroimaging studies have revealed a possible relationship between morphological brain changes and the manifestation of psychiatric disorders such as depression, schizophrenia, and alcoholism. Although its biological mechanism is still unclear, the emerging evidence suggests that the alteration of neurogenesis is the key factor for the morphological brain changes of these psychiatric disorders. In our previous work, we analyzed the mechanism of neural network disruption by ethanol using cultured cells, and found a suppressive effect of ethanol on neural stem cell (NSC) differentiation. While, we also demonstrated that antidepressants, mood stabilizers and atypical antipsychotics stimulate NSC differentiation which was inhibited by ethanol. In the present work, we have demonstrated that the usefulness of intravenous transplantation of NSCs to fetal alcohol spectrum disorder (FASD) model rat for the purpose of reconstructing the impaired neural network and investigating the possibility of regenerative therapy for patients with neurobehavioral deficits of FASD. We have shown the potential migration of transplanted NSCs into the brain by visualizing a fluorescent cell marker and radioisotope, as well as the possible recovery of behavioral abnormalities observed in FASD model rats, such as memory/cognitive function, and social interaction. We further assessed the characteristics of transplanted cells in the brain and found that the GABAergic interneurons were increased in amygdale, DG, cingulated cortex areas in the model rat. In the amygdala and cingulate Cortex of model rats, number of parvalbumin positive cells was reduced and the NSC transplantation recovered these disturbances. Moreover, in the amygdala and cingulate cortex, intravenous NSC transplantation appears to regenerate expression of post-synaptic density protein 95 (PSD95) in FASD model rats. These results indicate that intravenous NSC transplantation has the potential to become a therapeutic intervention for FASD patients.