HMGB1, TLR2 and TLR4 expression in cellular models of Huntington’s disease

MATEO PALMIERI; FEDERICO LÓPEZ COUSELO; JULIETA SABA; DIEGO RIVAS; MARÍA FRISER; LILA CARNIGLIA; DANIELA DURAND; MERCEDES LASAGA; CARLA CARUSO

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2023

Sociedad Argentina de Investigación Clínica

Huntington’s disease is a neurodegenerative genetic disorder caused by a CAG repeat expansion in the huntingtin genethat generates motor, cognitive, and psychiatric symptoms in humans. 3NP is a toxin that generates mitochondrialdysfunction like HD. In glial cells, oxidative stress can cause an inflammatory response. HMGB1 is a nuclear protein thatregulates gene expression and participates in DNA repair. HMGB1 can bind to toll-like receptors (TLR) and trigger aninflammatory response. We investigated the expression of HMGB1 and its receptors in zQ175 knock-in mouse model ofHD (HD mice). The expression of HMGB1 and its receptors was determined in cultures of astrocytes and microglia fromWT and HD mice striatum and cortex. By immunocytochemistry, we demonstrated that the expression of HMGB1 andTLR4 increases in cortical HD microglia (p0.05), while the expression ofTLR2 in both cell types remains unchanged (p>0.05). We evaluated the expression of C1qA only in microglia and WTand HD cortex microglia showed no differences in its expression (p>0.05). Our findings show that serum deprivationincreases the expression of HMGB1 in astrocytes and HD microglia (p