IL-1β-mediated macrophage infiltration into the brain after peripheral tissue injury

Abstract

Background: Infiltration of macrophages into the central nervous system (CNS) is involved in many neurological disorders, such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and autism. Despite extensive studies into neuroinflammation associated macrophage infiltration into the CNS, its underlying mechanisms and pathological roles remain unclear, especially when triggered by peripheral inflammation. Methods: To further elucidate the role and mechanism of peripheral inflammation in neurological disorders, we exploited interleukin 1 beta (il1b) mutant transgenic zebrafish (Danio rerio) with fluorescent protein expression restricted to macrophages to track the macrophage migration under peripheral inflammation following tail amputation. Results: We found that macrophage infiltration into the brain of zebrafish embryo following peripheral tissue injury can be alleviated via genetically targeting il1b. In addition, through circulation-independent migration, macrophages infiltrate brains with evidence of increased apoptosis. We further identified the expression of camk2g1 in the brains of zebrafish with hyperactive behavior following peripheral tissue injury. This il1b-regulated protein is associated with neuropsychiatry disorders. Conclusion: These findings demonstrated that peripheral tissue injury induces il1b-mediated macrophage infiltration into the brain and a hyperactive behavior.