Abstract
BackgroundHibernation is a state of extremely reduced physiological functions and a deep depression of CNS activity. We have previously shown that the histamine levels increase in the brain during hibernation, as does the ratio between histamine and its first metabolite, suggesting increased histamine turnover during this state. The inhibitory histamine H3 receptor has both auto- and heteroreceptor function, rendering it the most likely histamine receptor to be involved in regulating the activity of histamine as well as other neurotransmitters during hibernation. In view of accumulating evidence that there is a global depression of transcription and translation during hibernation, of all but a few proteins that are important for this physiological condition, we reasoned that an increase in histamine H3 receptor expression would clearly indicate an important hibernation-related function for the receptor.ResultsIn this study we show, using in situ hybridization, that histamine H3 receptor mRNA increases in the cortex, caudate nucleus and putamen during hibernation, an increase that is accompanied by elevated receptor binding in the cerebral cortex, globus pallidus and substantia nigra. These results indicate that there is a hibernation-related increase in H3 receptor expression in cortical neurons and in striatopallidal and striatonigral GABAergic neurons. GTP-γ-S binding autoradiography shows that the H3 receptors in the globus pallidus and substantia nigra can be stimulated by histamine throughout the hibernation cycle, suggesting that they are functionally active during hibernation.ConclusionsThese results show that the histamine H3 receptor gene is one of the few with a transcript that increases during hibernation, indicating an important role for the receptor in regulating this state. Moreover, the receptor is functionally active in the basal ganglia, suggesting a function for it in regulating e.g. dopaminergic transmission during hibernation.
Highlights
Hibernation is a state of extremely reduced physiological functions and a deep depression of central nervous system (CNS) activity
Importantly, we were able to delay arousal from hibernation by infusing histamine into the hippocampus of hibernating ground squirrels [5]. These findings suggest an important role for histamine in hibernation, wherein increased activity of histamine-releasing neurons is an important component of the CNS mechanism that produces and/or maintains the hibernating state
Histamine H3 receptor mRNA expression Among the areas of the ground squirrel brain included in this study, the histamine H3 receptor mRNA expression was highest in the cortex, caudate nucleus and the putamen, low in the globus pallidus and lowest in the substantia nigra (Fig 1A,1B,1C,1D,1E,1F)
Summary
Hibernation is a state of extremely reduced physiological functions and a deep depression of CNS activity. The inhibitory histamine H3 receptor has both autoand heteroreceptor function, rendering it the most likely histamine receptor to be involved in regulating the activity of histamine as well as other neurotransmitters during hibernation. In view of accumulating evidence that there is a global depression of transcription and translation during hibernation, of all but a few proteins that are important for this physiological condition, we reasoned that an increase in histamine H3 receptor expression would clearly indicate an important hibernation-related function for the receptor. Hibernation is a physiological state characterized by extreme reductions in body temperature and metabolic rate that reduce energy expenditure during seasons of cold ambient temperature and food shortage. The question arises as to what neurochemical changes occur to produce the hibernating state
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