TY - JOUR

T1 - Experimental sickness reduces hypocretin receptor 1 expression in the lateral hypothalamus and ventral tegmental area of female mice

AU - Kolmos, Mie Gunni

AU - Arribas, Alba Pérez

AU - Kornum, Birgitte Rahbek

AU - Justinussen, Jessica Lauren

N1 - Publisher Copyright: © 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - Recent studies have focused on how sickness behaviours, including lethargy, are coordinated in the brain in response to peripheral infections. Decreased hypocretin (orexin) signalling is associated with lethargy and previous research suggests that hypocretin signalling is downregulated during sickness. However, there are studies that find increases or no change in hypocretin signalling during sickness. It is further unknown whether hypocretin receptor expression changes during sickness. Using lipopolysaccharide (LPS) to induce sickness in female mice, we investigated how LPS-injection affects gene expression of hypocretin receptors and prepro-hypocretin as well as hypocretin-1 peptide concentrations in brain tissue. We found that hypocretin receptor 1 gene expression was downregulated during sickness in the lateral hypothalamus and ventral tegmental area, but not in the dorsal raphe nucleus or locus coeruleus. We found no changes in hypocretin receptor 2 expression. Using a gene expression calculation that accounts for primer efficiencies and multiple endogenous controls, we were unable to detect changes in prepro-hypocretin expression. Using radioimmunoassay, we found no change in hypocretin-1 peptide in rostral brain tissue. Our results indicate that hypocretin receptor expression can fluctuate during sickness, adding an additional level of complexity to understanding hypocretin signalling during sickness.

AB - Recent studies have focused on how sickness behaviours, including lethargy, are coordinated in the brain in response to peripheral infections. Decreased hypocretin (orexin) signalling is associated with lethargy and previous research suggests that hypocretin signalling is downregulated during sickness. However, there are studies that find increases or no change in hypocretin signalling during sickness. It is further unknown whether hypocretin receptor expression changes during sickness. Using lipopolysaccharide (LPS) to induce sickness in female mice, we investigated how LPS-injection affects gene expression of hypocretin receptors and prepro-hypocretin as well as hypocretin-1 peptide concentrations in brain tissue. We found that hypocretin receptor 1 gene expression was downregulated during sickness in the lateral hypothalamus and ventral tegmental area, but not in the dorsal raphe nucleus or locus coeruleus. We found no changes in hypocretin receptor 2 expression. Using a gene expression calculation that accounts for primer efficiencies and multiple endogenous controls, we were unable to detect changes in prepro-hypocretin expression. Using radioimmunoassay, we found no change in hypocretin-1 peptide in rostral brain tissue. Our results indicate that hypocretin receptor expression can fluctuate during sickness, adding an additional level of complexity to understanding hypocretin signalling during sickness.

KW - home-cage behaviour

KW - lipopolysaccharide

KW - locomotor activity

KW - orexin

KW - qPCR

KW - radioimmunoassay

U2 - 10.1111/ejn.16151

DO - 10.1111/ejn.16151

M3 - Journal article

C2 - 37818927

AN - SCOPUS:85173632060

VL - 58

SP - 4002

EP - 4010

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 9

ER -