The histaminergic system in the brain: structural characteristics and changes in hibernation

Histaminergic neurons in adult vertebrate brain are confined to the posteri or hypothalamic area, where they are comprised of scattered groups of neuro ns referred to as the tuberomammillary nucleus. Histamine regulates hormona l functions, sleep, food intake, thermoregulation and locomotor activity, f or example. In the zebrafish, Danio rerio, histamine was detected only in t he brain, where also the histamine synthesizing enzyme L-histidine decarbox ylase (HDC) was expressed. It is possible that histamine has first evolved as a neurotransmitter in the central nervous system. We established sensiti ve quantitative in situ hybridization methods for histamine H-1 and H-2 rec eptors and HDC, to study the modulation of brain histaminergic system under pathophysiological conditions. A transient increase in H-1 receptor expres sion was seen in the dentate gyrus and striatum after a single injection of kainic acid, a glutamate analog. H-1 antagonists are known to increase dur ation of convulsions, and increased brain histamine is associated with redu ced convulsions in animal models of epilepsy. No HDC mRNA was detected in b rain Vessels by in situ hybridization, which suggests lack of histamine syn thesis by brain endothelial cells. This was verified by lack of HDC mRNA in a rat brain endothelial cell line, RBE4 cells. Both H-1 and H-2 receptor m RNA was found in this cell line. and the expression of both receptors was d ownregulated by dexamethasone. The findings are in agreement with the conce pt that histamine regulates blood-brain barrier permeability through H-1 an d H-2 receptor mediated mechanisms. Hibernation is characterized by a drast ic reduction of central functions. The activity of most transmitter systems is maintained at a very low level. Surprisingly, histamine levels and turn over were clearly elevated in hibernating ground squirrels, and the density of histamine-containing fibers was higher than in euthermic animals. It is possible that histamine actively maintains the low activity of other trans mitters during the hibernation state. (C) 2000 Elsevier Science B.V. All ri ghts reserved.