The PICK1/TLR4 complex on microglia is involved in the regulation of LPS-induced sepsis-associated encephalopathy.

The treatment options for sepsis-associated encephalopathy caused by systemic inflammation are still not sufficient. Protein kinase C interaction protein 1 (PICK1) has attracted much attention because of its important physiological functions in many tissues. However, its role in sepsis-associated encephalopathy remains elusive. Our study results revealed that the expression levels of PICK1 protein in mice with lipopolysaccharide-induced sepsis-associated encephalopathy were not significantly changed, but PICK1 deficiency led to excessive activation of microglia and Toll-like receptor (TLR)4 pathways, which aggravated the sepsis- associated encephalopathy. We also observed that PICK1 and TLR4 form a complex in microglial cells, thereby providing brain protection. These findings contribute to our understanding of the important role of PICK1 in sepsis and may provide novel therapeutic targets to treat sepsis-associated encephalopathy.