Periodic properties of the histaminergic system of the mouse brain

Abstract

Brain histamine is involved in the regulation of the sleep-wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1-methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine-N-methyltransferase in C57BL/6J mice. In the C57BL/6J strain, histamine release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24-h periodicity was observed. Brain tissue 1-methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine-N-methyltransferase in the striatum and cortex did not show a 24-h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12-h periodicity. These results show that the activities of histamine-metabolizing enzymes are not under simple direct circadian regulation. The complex and non-uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness.

Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

“…It is conceivable that NST adrenergic fibers projecting to the TMN disinhibit TMN neurons that in turn facilitate oxytocin release from the PVN to mediate OEA's prosatiety effect. Indeed, OEA increased c-Fos expression in a subgroup of TMN neurons, corresponding to the E2/E3 region in the mouse (35), that presumably are organized in a functionally distinct circuit, impinging on selected brain regions (36). c-Fos/HDC double-immunoreactive neurons in food-deprived mice were few, which is consistent with results obtained in rats under scheduled feeding (37).…”

Distribution of histaminergic neuronal cluster in the rat and mouse hypothalamus

“…In summary, E1 is a cluster reported to functionally shift circadian regulation to a greater degree than E2 (I'Anson et al, 2011), whereas these two clusters appear to be organized into a single functional complex. Moreover, extrahypothalamic HDCi neuronal clusters were also observed around the basal ganglia corroborating previous studies (Ito et al, 1996;Krusong et al, 2011;Pollard et al, 1985;Rozov et al, 2014).…”

A Systematic Search and Mapping Review of Studies on Intracerebral Microdialysis of Amino Acids, and Systematized Review of Studies on Circadian Rhythms

“…Average histamine concentrations were higher during dark than during light. Rozov et al kept mice on a 12:12 light-dark cycle; lights ON at 20:30, and collected dialysate for five consecutive days [38]. Data were analysed with the Lomb–Scargle method using LSP software.…”

“…To conclude, histamine seems consistently higher during the dark than during the light phase in the hypothalamus in mice and in several brain regions in rats [343536373839]. …”