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Review
. 2020 Feb 5:14:23.
doi: 10.3389/fnins.2020.00023. eCollection 2020.

Complement System in Brain Architecture and Neurodevelopmental Disorders

Juliana Magdalon  1   2 , Fernanda Mansur  1 , André Luiz Teles E Silva  1   3 , Vitor Abreu de Goes  1   2 , Orly Reiner  4 , Andréa Laurato Sertié  1
Affiliations
Review

Complement System in Brain Architecture and Neurodevelopmental Disorders

Juliana Magdalon et al. Front Neurosci. .

Abstract

Current evidence indicates that certain immune molecules such as components of the complement system are directly involved in neurobiological processes related to brain development, including neurogenesis, neuronal migration, synaptic remodeling, and response to prenatal or early postnatal brain insults. Consequently, complement system dysfunction has been increasingly implicated in disorders of neurodevelopmental origin, such as schizophrenia, autism spectrum disorder (ASD) and Rett syndrome. However, the mechanistic evidence for a causal relationship between impaired complement regulation and these disorders varies depending on the disease involved. Also, it is still unclear to what extent altered complement expression plays a role in these disorders through inflammation-independent or -dependent mechanisms. Furthermore, pathogenic mutations in specific complement components have been implicated in the etiology of 3MC syndrome, a rare autosomal recessive developmental disorder. The aims of this review are to discuss the current knowledge on the roles of the complement system in sculpting brain architecture and function during normal development as well as after specific inflammatory insults, such as maternal immune activation (MIA) during pregnancy, and to evaluate the existing evidence associating aberrant complement with developmental brain disorders.

Keywords: complement system; neural progenitor proliferation; neurodevelopmental disorders; neurogenesis; neuronal migration; synapse refinement.

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Figures

FIGURE 1
FIGURE 1
Complement activation pathways and the activity or expression of their individual components (either protein or mRNA) in schizophrenia and autism spectrum disorder (ASD). ↑ red, increased protein activity or expression in blood from patients; ↓ red, decreased protein activity or expression in blood from patients; ↑ blue, increased RNA expression in brain tissues from patients; ↓ blue, decreased RNA expression in brain tissues from patients (Spivak et al., 1989, 1993; Warren et al., 1994; Wong et al., 1996; Maes et al., 1997; Shcherbakova et al., 1999; Hakobyan et al., 2005; Mayilyan et al., 2006; Corbett et al., 2007; Boyajyan et al., 2010; Momeni et al., 2012; Nardone et al., 2014; Li et al., 2016; Sekar et al., 2016; Fagan et al., 2017; Shen et al., 2018). The Figure does not distinguish between strong and weak evidence.
See this image and copyright information in PMC

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