Loss of the Sexually Dimorphic Neuro-Inflammatory Response in a Transgenic Mouse Model of Huntington’s Disease

Background We previously reported sex differences in depression-like behaviours in a mouse model of Huntington's disease (HD). Objective We hypothesized that immune response could also be altered in HD mice in a sex-dependent manner. Methods Here, we assessed the molecular effects of an acute challenge with lipopolysaccharides (LPS) in female versus male R6/1 transgenic HD mice. Results We found an enhancement of LPS-induced TNF-α gene expression in the hypothalamus of female HD mice. TNF-α serum levels following LPS administration were also higher in female HD mice compared to WT animals. In contrast, male HD mice exhibited reduced LPS-induced TNF-α gene expression compared to WT animals. Discussion Our findings suggest that immune response to LPS is altered in HD mice in a sex-dependent manner. These pro-inflammatory abnormalities may contribute to the sexually dimorphic depression-like behaviours displayed by this mouse model of HD.