Sex-Differences Influence Depressive-Like Behaviour via Alterations in Microglial Expression of GIF-1, TREM2, and IL-1β in an Acute Lipopolysaccharide-Induced Murine Neuroinflammation Model.

Abstract

Background: Neurodegenerative diseases (NDs) have caused serious health issues worldwide. A growing body of evidence suggests a correlation between neuroinflammation and abnormal microglial activity with ND symptoms. Microglia survey play crucial roles in CNS during health and the injury. It is proposed that sex affects microglial roles during inflammation, resulting in mouse behavioural changes and expression alterations in key markers related to microglia functions.

Methods: Male and female C57BL/6 mice were injected with a single dose of LPS (5 mg/kg, i.p.) or saline. After 48 h, an open field test was conducted, followed by brain tissues collection for measuring the expression of IGF-1, IL-1β and TREM2 and Immunohistochemistry (IHC) analysis for NLRP3 level.

Results: Males displayed greater depressive-like behaviour in the OFT, with lower levels of IGF-1, IL-1β, and NLRP3 and high TREM2 expression. Female mice did not exhibit this behaviour, in contrast to male mice, they exhibited increased IL-1β and NLRP3 expression.

Discussion: This study revealed that LPS-induced sex-specific changes in genes involved in neuronal cell survival caused behavioural alterations in male mice. Moreover, females had observed inflammatory responses that had no impact on behavioural alterations. Overall, both sexes exhibited sex-specific microglial activation states.