Paying the circadian toll: the circadian response to LPS injection is dependent on the TLR4 receptor.

PALADINO, N; LEONE, MJ; PLANO, SA; GOLOMBEK, DA

JOURNAL OF NEUROIMMUNOLOGY

ELSEVIER SCIENCE BV

Año: 2010 vol. 225 p. 62 - 67

0165-5728

Systemic low doses of the endotoxin lipopolysaccharide (LPS) administered at CT15 (Circadian Time 12 corresponds to locomotor activity onset) induce phase-delays of locomotor activity rhythms in mice. To evaluate if this effect was mediated by the toll-like receptor 4 (TLR4), our present aim was to characterize the circadian behavior and LPS-induced circadian response of TLR4 (LPS receptor)-deficient mice (in C57bl/10 and C3H backgrounds). In mutants, we observed a free-running period and a light-induced phase-delay similar to the one observed in their corresponding wild-type (WT) littermates. The LPS-induced phase-delay, wheel-running inhibition and c-Fos/Per-1 immunoreactivity in the paraventricular hypothalamic nucleus observed in WT mice was absent or significantly decreased in TLR4-deficient mice. In conclusion, we show that LPS-induced circadian responses are mediated by TLR4.