Comparative Analysis of the Responses of Orexin-Containing Neurons to Administration of Different Doses of Lipopolysaccharide

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

“…Grossberg and colleagues found no change in Hcrt‐1 in CSF 3 h after LPS challenge, but a significant decrease after 13 h (Grossberg et al, 2011). Perekrest looked at the number of hypocretin positive cells, which relies on detection of Hcrt‐1 peptide, and found no effect 2 and 4 h after LPS, but a decrease 6 h after LPS challenge (Perekrest et al, 2008, 2011). These findings suggest that there is a decrease in Hcrt‐1 peptide after the onset of sickness behaviour.…”

“…Hcrt‐1 peptide is generally lower in rostral brain sections during the light phase and higher during the dark phase in nocturnal animals (Justinussen et al, 2015) meaning less statistical power is needed to detect increases during the light phase and decreases during the dark phase as opposed to changes in the opposite direction at the respective time of day. Perekrest and colleagues showed an increase in hypocretin positive neurons in two different doses during the light phase (Perekrest et al, 2011). In another study, they also suggest increases in prepro‐Hcrt in early sickness (Perekrest et al, 2013).…”

“…Other studies report both increases and decreases in hypocretin signalling in response to LPS, depending on time of day or duration of sickness (Gaykema & Goehler, 2009; Perekrest et al, 2011). These two studies report both increases and decreases in hypocretin signalling using two separate measures (cFos and Hcrt‐1 positive neurons, respectively).…”

“…Therefore, it is still unclear how hypocretin fluctuates during sickness. Previous studies measuring hypocretin in response to LPS‐injection vary in time of day, time since injection, dose of LPS, and hypocretin measurement, which may explain some discrepancies (Gaykema & Goehler, 2009; Grossberg et al, 2011; Perekrest et al, 2008, 2011, 2013). While these studies have explored prepro‐hypocretin (prepro‐Hcrt) mRNA, Hcrt‐1 peptide in CSF, and cFos expression of hypocretin neurons during sickness, we have not found any studies that investigated how hypocretin receptors are regulated in response to LPS.…”

Brain Reactions Caused by Administration of Antigen

“…LPS administration in a dose of 25 mg/kg causes an increase in quantity of orexin-positive neurons 2 and 4 hours after injection (Fig. 4) [80]. The increase or decrease of orexin content in neurons indicates a shift in balance between synthesis and utilization of this neuropeptide e.g.…”