Melatonin from slow-release implants did not influence the gene expression of the lipopolysaccharide receptor complex in the choroid plexus of seasonally anoestrous adult ewes subjected or not to a systemic inflammatory stimulus

Abstract This study was designed to determine the effect of melatonin from continuous slow-release implants on (i) the mRNA expression for the lipopolysaccharide (LPS) receptor complex, which includes toll-like receptor 4 (TLR4), myeloid differentiation-2 factor (MD-2) and cluster of differentiation-14 (CD14) in the choroid plexus (CP) and (ii) on the plasma concentration of LPS binding protein (LBP) in ewes subjected or not to a systemic inflammatory stimulus (intravenous injection of LPS). Experiments were conducted in ovariectomized, oestradiol-implanted ewes during seasonal anoestrus (May/June). In experiment 1, the ewes were divided into four groups: sham-implanted and placebo-treated (C/C), melatonin-implanted and placebo-treated (M/C, Melovine 18 mg), sham-implanted and LPS-treated for 3 h (C/LPS, 400 ng/kg of body mass) and melatonin-implanted and LPS-treated for 3 h (M/LPS). In experiment 2, the ovariectomized ewes were melatonin-implanted or sham-implanted and treated with LPS for 6 h (M/LPS and C/LPS, respectively). Plasma melatonin concentrations reached 4.5 ± 1.5 pg/ml in the C/C group, 151.4 ± 56.4 pg/ml in the M/C group, 7.8 ± 4.3 pg/ml in the C/LPS group and 240.6 ± 93.0 pg/ml in the M/LPS group one month after melatonin or sham implantation. Plasma cortisol concentrations remained at basal level throughout the experiment in the control ewes (C/C and M/C), whereas in the LPS-treated ewes, mean cortisol concentrations increased from 13.7 ± 2.4 ng/ml to 92.0 ± 10.2 ng/ml and from 15.4 ± 5.9 ng/ml to 100.0 ± 10.7 ng/ml in the C/LPS and M/LPS groups, respectively. The LPS treatment significantly (p ≤ 0.05) increased the mRNA expression for TLR4 and CD14 but had no effect on the MD-2 mRNA expression in the C/LPS and M/LPS groups. Plasma LBP concentration was not affected within 3 h of the LPS-treatment (experiment 1) but increased significantly at 4–6 h after LPS-treatment in the C/LPS and M/LPS groups (experiment 2). Melatonin from the slow-release implants did not change the mRNA expression of all the examined genes or the plasma LPB concentration. These results allow us to infer that melatonin implantation does not disturb the CP potential to detect the specific microbial components derived from gram-negative bacteria.