No loss of orexin/hypocretin, melanin-concentrating hormone, or locus coeruleus noradrenergic neurons in a rat model of chronic sleep restriction.

Chronic sleep restriction (CSR) is common in modern society, adversely affecting cognitive performance and health. Yet how it impacts neurons regulating sleep remains unclear. Several studies using mice reported substantial losses of wake-active orexin/hypocretin and locus coeruleus (LC) noradrenergic neurons, but not rapid eye movement sleep-active melanin-concentrating hormone (MCH) neurons, following CSR. Here we used immunohistochemistry and stereology to examine orexin, MCH, and LC noradrenergic neurons in a rat model of CSR that uses programmed wheel rotation (3 hours on/1 hour off; '3/1' protocol). Adult male Wistar rats underwent 1 or 4 cycles of the 4-day 3/1 CSR protocol, with 2-day recovery between cycles in home cages. Time-matched control rats were housed in locked wheels/home cages. We found no significant differences in the numbers of orexin, MCH, and LC noradrenergic neurons following either 1- or 4-cycle CSR protocol compared to respective controls. Similarly, the 4-cycle CSR protocol had no effect on the densities of orexin axon terminals in the LC, noradrenergic dendrites in the LC, and noradrenergic axon terminals in the frontal cortex. Body weights, however, decreased after 1 cycle of CSR, and then increased with diminishing slope over the next 3 cycles. Thus, we found no evidence for loss of orexin or LC noradrenergic neurons following 1 and 4 cycles of the 4-day 3/1 CSR protocol in rats. Differences in CSR protocols and/or possible species differences in neuronal vulnerability to sleep loss may account for the discrepancy between the current results in rats and previous findings in mice. This article is protected by copyright. All rights reserved.