Mscs-derived evs as potential treatment in a phencyclidine model of schizophrenia

Abstract

Background & Aim Schizophrenia is a debilitating mental disorder, a major contributor to the global health burden of disease. Although antipsychotic medication is very effective against the positive symptoms of the disease, such as hallucinations, such an effective treatment for the negative symptoms is not available. Phencyclidine (PCP) has been validated in rodents as a model for schizophrenia, shown to reliably induce both positive and negative symptoms in a multitude of behavioral tests. It was previously shown in our lab that behavioral phenotypes of PCP-treated mice can be alleviated after intracranial transplantation of mesenchymal stem cells (MSC). Methods, Results & Conclusion In this study, we assessed the feasibility of intranasal delivery of MSCs-derived EVs to improve the positive and negative symptoms in a PCP model of schizophrenia. Our results show that mice treated with MSCs-EVs are beneficial for preventing both positive and negative symptoms in a PCP-model of schizophrenia. While PCP-treated mice showed a deficiency in social interaction and increased vulnerability to amphetamine, mice co-administered with PCP and MSCs-EVs behaved similarly to the sham group, treated with saline. Immunohistochemical studies demonstrated that the EVs prevented loss of Paravalbumin-expressing GABAergic neurons in the PFC of treated mice, where EVs were most congregated. We believe MSCs-derived EVs may be an invaluable treatment for schizophrenia. With the convenient intranasal administration and ability to arrive at the site of damage in the diseased brain, they may offer an unprecedented improvement in negative symptoms.