Messenger RNA for neuropeptide Y in the arcuate nucleus increases in parallel with plasma adrenocorticotropin during sepsis in the rat

Abstract

Loss of appetite occurs in the cecal ligation and puncture (CLP) model of sepsis in conjunction with the activation of central neural stress pathways. Neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus is upregulated by several stressors and is stimulatory to feeding. To examine the response of NPY messenger RNA in the arcuate nucleus to sepsis, we used biotinylated RNA probes and a quantitative non-isotopic in situ hybridization approach in cryo-preserved sections from rats made septic by CLP. The mRNA in arcuate neurons was upregulated from the first day after CLP. By the afternoon of the third day through the morning of the fourth day, the average grey level of NPY mRNA clusters was 30% greater after CLP than after sham surgery (P < 0.05), and the integrated optical density based on both the grey level and the amount of area with detectable mRNA was 60% greater after CLP than after sham surgery (P < 0.03). Both the average grey level and area with detectable staining were positively correlated to plasma ACTH (r = 0.953 and r = 0.917, respectively, n = 10 and P < 0.01 in each case). Thus sepsis increases the expression of the mRNA for NPY in the arcuate nucleus in proportion to the magnitude of the stress response. However, the suppression of feeding behavior in the CLP model suggests that sepsis activates additional mechanisms that negate the orexigenic contribution of the neuronal increase in NPY mRNA. Keywordsadrenocorticotropin; arcuate nucleus; cecal ligation and puncture; in situ hybridization; neuropeptide Y; sepsis Sepsis as a result of bacterial or fungal infection is a potentially lethal complication in critically illness that leads to the suppression of appetite and negative nitrogen balance with a loss in body mass [7]. These metabolic effects result in part from the response of central stress §Present Address of Corresponding

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“…The riboprobe was generated from a cDNA clone by PCR and labeled with 16-biotinylated-dUTP (Roche Diagnostics Corp.; Indianapolis, IN). Hybridization to sections of mouse ovary was carried out as described previously (Berghorn et al 2001;Koban et al 2006;Carlson et al 2009). Briefly, 25-µm sections from the ovaries of mice perfused with 2.5% acrolein in 4% buffered paraformaldehyde were maintained in cryoprotectant at −20C.…”

The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour

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