Emerging Roles of Complement in Psychiatric Disorders.

Mélanie Druart,Corentin Le Magueresse

doi:10.3389/fpsyt.2019.00573

Mélanie Druart, Corentin Le Magueresse

Open Access

https://doi.org/10.3389/fpsyt.2019.00573

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Abstract

The complement system consists of more than 30 proteins that have long been known to participate to the immune defence against pathogens and to the removal of damaged cells. Their role, however, extends beyond immunity and clearance of altered “self” components in the periphery. In particular, complement proteins can be induced by all cell types in the brain. Recent discoveries highlight the role of complement in normal and pathological brain development. Specifically, the complement system mediates synaptic pruning, a developmental process whereby supernumerary synapses are eliminated in the immature brain. The complement system has been implicated in pathological synapse elimination in schizophrenia, West Nile virus infection, and lupus, all of which are associated with psychiatric manifestations. Complement also contributes to synapse loss in neurodegenerative conditions. This review provides a brief overview of the well-studied role of complement molecules in immunity. The contribution of complement to embryonic and adult neurogenesis, neuronal migration, and developmental synaptic elimination in the normal brain is reviewed. We discuss the role of complement in synapse loss in psychiatric and neurological diseases and evaluate the therapeutic potential of complement-targeting drugs for brain disorders.

Highlights

The link between immunogenetics, inflammation, and several major psychiatric disorders such as Schizophrenia (SZ), Bipolar Disorder (BD), and Autism Spectrum Disorder (ASD) is well substantiated [1,2,3,4,5]
Since the classical complement pathway is involved in microglia-dependent synaptic pruning in the healthy brain, it has been proposed that the complement system may directly or indirectly stimulate the type I interferon pathway to promote synapse engulfment and elimination by microglia in Systemic lupus erythematosus (SLE) [94]
C1q-deficient mice are protected from Aβ-dependent synapse loss. These data suggested that the developmental pruning pathway is re-activated at the preplaque in Alzheimer’s disease (AD), prompting the authors to test whether Aβ-dependent synapse loss is present in mice lacking CR3, a complement receptor only expressed by microglia in the brain

Summary

Introduction

The link between immunogenetics, inflammation, and several major psychiatric disorders such as Schizophrenia (SZ), Bipolar Disorder (BD), and Autism Spectrum Disorder (ASD) is well substantiated [1,2,3,4,5]. More recent studies have shown that neural cells express complement molecules throughout embryonic and postnatal development in rodent and human brain tissue (Table 1) [25, 33,34,35]. Proteins that have homology with C1q but are not involved in the leptin, classical, or alternative pathways are expressed in the brain and participate in synapse formation, maintenance, and function.

Results

Conclusion