New Insights Regarding Diagnosis and Medication for Schizophrenia Based on Neuronal Synapse-Microglia Interaction

Abstract

Schizophrenia is a common psychiatric disorder that usually develops during adolescence and young adulthood. Since genetic and environmental factors are involved in the disease, the molecular status of the pathology of schizophrenia differs across patients. Recent genetic studies have focused on the association between schizophrenia and the immune system, especially microglia-synapse interactions. Microglia physiologically eliminate unnecessary synapses during the developmental period. The overactivation of synaptic pruning by microglia is involved in the pathology of brain disease. This paper focuses on the synaptic pruning function and its molecular machinery and introduces the hypothesis that excessive synaptic pruning plays a role in the development of schizophrenia. Finally, we suggest a strategy for diagnosis and medication based on modulation of the interaction between microglia and synapses. This review provides updated information on the involvement of the immune system in schizophrenia and proposes novel insights regarding diagnostic and therapeutic strategies for this disease.

Keywords: CX3CR1; complement; diagnosis; medication; microglia; schizophrenia; synaptic pruning.

Figure 1

An overview of systemic complement activation. The complement system is composed of nine main components (C1–C9) and regulatory factors. Immunological functions are conducted by three pathways: the classical, alternative, and lectin pathways. In these pathways, enzymatic chain reactions of the complements proceed to finally form a membrane attack complex to destroy bacteria and virus-infected cells. MASP, mannose-binding protein-associated serine protease; FD, factor D; FB, factor B; Bb, factor Bb; P, properdin.

Figure 2

The microglial synaptic pruning in schizophrenia. (a) Microglia exhibit hyper-ramified morphology in schizophrenia due to genetic and environmental factors. (b) Healthy microglia eliminate complement-tagged synapses with lower activity. In schizophrenia, hyper-ramified microglia prune healthy synapses by the excessive activation of complements.