Complex Neuroimmune Involvement in Neurodevelopment: A Mini-Review

Abstract

It is increasingly evident that cells and molecules of the immune system play significant roles in neurodevelopment. As perinatal infection is associated with the development of neurodevelopmental disorders, previous research has focused on demonstrating that the induction of neuroinflammation in the developing brain is capable of causing neuropathology and behavioral changes. Recent studies, however, have revealed that immune cells and molecules in the brain can influence neurodevelopment without the induction of overt inflammation, identifying neuroimmune activities as integral parts of normal neurodevelopment. This mini-review describes the shift in literature that has moved from emphasizing the intrusion of inflammatory events as a main culprit of neurodevelopmental disorders to evaluating the deviation of the normal neuroimmune activities in neurodevelopment as a potential pathogenic mechanism.

Keywords: cytokine; glia; neurodevelopmental disorders; neuroinflammation.

Figure 1

Schematic diagram showing neuroimmune activities involved in neurodevelopment. Microglia and astrocytes play a role in appropriate neurodevelopment and contribute to the pathophysiology of neurodevelopmental diseases. In frank inflammation, which is stimulated by perinatal immune activation, astrocytes and microglia are activated by immune stimulus. This activation leads to production of proinflammatory cytokines (TNFa, IL-1β) and damage to the blood–brain barrier. Infiltration of immune cells to the brain parenchyma together with astrocyte and microglial activation results in neuronal damage. Under physiological conditions, astrocytes and microglia play critical roles during neurodevelopment and homeostasis. Astrocyte- and microglia-driven cytokines regulate 5 critical processes of neurodevelopment that are crucial for developing a healthy brain: neuronal proliferation, synaptogenesis, synaptic pruning, neuronal migration, and neural circuitry regulation. Created with BioRender.com.