Immune synaptopathies: how maternal immune activation impacts synaptic function during development

In the last two decades, the term synaptopathy has been largely used to underline the concept that impairments of synaptic structure and function are the major determinant of brain disorders, including neurodevelopmental disorders. This notion emerged from the progress made in understanding the genetic architecture of neurodevelopmental disorders, which highlighted the convergence of genetic risk factors onto molecular pathways specifically localized at the synapse. However, the multifactorial origin of these disorders also indicated the key contribution of environmental factors. It is well recognized that inflammation is a risk factor for neurodevelopmental disorders, and several immune molecules critically contribute to synaptic dysfunction. In the present review, we highlight this concept, which we define by the term immune-synaptopathy, and we discuss recent evidence suggesting a bi-directional link between the genetic architecture of individuals and maternal activation of the immune system in modulating brain developmental trajectories in health and disease.

Automated summary

In the last two decades, the concept of synaptopathy has been widely used to emphasize that impairments of synaptic structure and function are the main determinant of brain disorders, including neurodevelopmental disorders. The understanding of the genetic architecture of these disorders has highlighted the convergence of genetic risk factors on synapse-related molecular pathways. However, the involvement of environmental factors and inflammation has also been recognized, with immune molecules contributing to synaptic dysfunction. This review discusses the concept of immune-synaptopathy and recent evidence suggesting a bidirectional link between genetic architecture and maternal immune system activation in modulating brain development.