BEHAVIORAL PROFILE AND NEUROIMMUNE MARKERS IN LIMBIC STRUCTURES OF TNFR1-DEFICIENT MICE EXPOSED TO LPS

The aim of this study was to evaluate whether the deletion of TNFR1 can protect against cognitive impairment induced by LPS administration. WT and TNFR1-/- mice (Animal Ethics Committee no. 1345200524) received LPS (1mg/kg) once daily, intraperitoneally, for three consecutive days. After the last administration, we performed behavioral tests on post-injection days (dpi) 3-8 (novel object recognition, elevated plus maze, fear conditioning, and conditioned fear extinction), followed by collection of structures (prefrontal cortex, amygdala, and hippocampus) for the measurement of IL-1beta and IL-10 levels. Data were analyzed by two-way ANOVA, followed by Bonferroni’s post-hoc test. Results were expressed as mean±SEM. We found no impairment in recognition memory, cue-related fear memory, and anxiety-like behavior. However, TNFR1 deletion caused a 47% decrease(11.09±1.99,p<0.05)in contextual fear memory compared to WT+SAL. LPS administration caused a 95.4% impairment in extinction learning in both genotypes(WT+SAL 24.369±1.900,p<0.05; TNFR1-/-SAL 23.738±2.793,p<0.05). Animals in the WT+LPS group had their learning normalized with a higher number of tone presentations compared to WT+SAL, while animals in the TNFR1-/-LPS group remained with fear expression increased by 70.2% until the end of the test, compared to the TNFR1-/-SAL group(19.047±2.998,p<0.05).We found a reduction in amygdala IL-10 expression in the TNFR1-/-LPS group(3.782±0.446 vs WT+SAL,p<0.05; TNFR1-/-LPS,p<0.05)and of IL-1beta in the amygdala(TNFR1-/-LPS:14.758±1.360,p<0.05)and prefrontal cortex(WT+LPS:14.288±3.029,p<0.05; TNFR1-/-LPS:5.355±0.605,p<0.01)of the LPS-treated groups. Our results suggest that the neuroinflammation model used does not affect anxiety-like behavior and memory expression, but impairs extinction learning, which may be related to the decreased expression of cytokines.