Abstract
A competition of neurobehavioral drives of sleep and wakefulness occurs during sleep deprivation. When enforced chronically, subjects must remain awake. This study examines histaminergic neurons of the tuberomammillary nucleus of the posterior hypothalamus in response to enforced wakefulness in rats. We tested the hypothesis that the rate-limiting enzyme for histamine biosynthesis, L-histidine decarboxylase (HDC), would be up-regulated during chronic rapid eye movement sleep deprivation (REM-SD) because histamine plays a major role in maintaining wakefulness. Archived brain tissues of male Sprague Dawley rats from a previous study were used. Rats had been subjected to REM-SD by the flowerpot paradigm for 5, 10, or 15 days. For immunocytochemistry, rats were transcardially perfused with acrolein-paraformaldehyde for immunodetection of L-HDC; separate controls used carbodiimide-paraformaldehyde for immunodetection of histamine. Immunolocalization of histamine within the tuberomammillary nucleus was validated using carbodiimide. Because HDC antiserum has cross-reactivity with other decarboxylases at high antibody concentrations, titrations localized L-HDC to only tuberomammillary nucleus at a dilution of ≥ 1:300,000. REM-SD increased immunoreactive HDC by day 5 and it remained elevated in both dorsal and ventral aspects of the tuberomammillary complex. Our results suggest that up-regulation of L-HDC within the tuberomammillary complex during chronic REM-SD may be responsible for maintaining wakefulness.
Highlights
In a general sense, higher animals are in one of two behavioral states: awake or asleep, with rapid transitions between them [1]
A lower magnification view of the ventral TMN (vTMN) of brain fixed with 4% carbodiimide and 5% paraformaldehyde is shown in Fig 2, panel A
In 1984, Panula described that antibodies raised using an immunogen of histamine conjugated to hemocyanin with carbodiimide identify histaminergic neurons as being localized in the posterior hypothalamus [52]
Summary
Higher animals are in one of two behavioral states: awake or asleep, with rapid transitions between them [1]. Sleep or a state comparable to mammalian sleep is highly conserved, being found across a remarkably wide range of phylogenies [2]. Despite there being a biological need for sleep or a sleep-like state, its evolutionary underpinnings and functions for homeostasis remain elusive [3], restoration of brain energy balance by sleep has been championed [4, 5]. That sleep is physiologically important is best exemplified by depriving an animal of sleep and observing the consequences during continued wakefulness. PLOS ONE | DOI:10.1371/journal.pone.0152252 December 20, 2016
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