Abstract
Immune activation in the prenatal and early postnatal periods is increasingly implicated in the aetiology of neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia, by disrupting critical neurodevelopmental processes. The impact of immune activation on brain development can be influenced by the type, timing, location, and severity of the infection. Viral, bacterial, and parasitic infections, as well as maternal autoimmune diseases, can lead to the activation of the purinergic P2X7 receptors, thereby contributing to neuroinflammation. Upon activation, P2X7 induces the assembly of the NLRP3 inflammasome, leading to the release of the pro-inflammatory cytokine IL-1β. Besides activation of additional inflammatory mediators, excessive IL-1β during critical periods of brain development can disrupt neuronal migration, synapse formation, dendritic morphology and blood-brain barrier integrity, contributing to a range of neurodevelopmental abnormalities. Animal studies have shown that inhibiting the components of the P2X7/NLRP3/IL-1β pathway can mitigate these adverse effects. This review examines the role of the P2X7/NLRP3/IL-1β pathway in mediating the effects of infection and neuronal inflammation on brain development. We discuss the therapeutic potential of targeting this pathway with a balanced approach that reduces long-term neuronal inflammation while preserving essential immune functions.