Age-related changes in histamine receptor mRNA levels in the mouse brain.

Several lines of evidence indicate that the histaminergic (HA) system is important for wakefulness and behavioral state regulation. We investigated the hypothesis that age-related changes in HA system occur which may be related to decreased alertness in aging. Although histidine decarboxylase mRNA levels did not change with age in C57BL/6 mice, significant differences were found in histamine H1 receptor (H1R), histamine H2 receptor (H2R), and histamine H3 receptor (H3R) mRNA levels in several brain regions. The most widespread changes were observed in H1R mRNA, which were significantly lower (27-38%) in the cortex, hypothalamus, hippocampus and medulla of 24-month-old mice relative to 3-month-old animals. Age-related changes in H2R mRNA levels were restricted to the pons and cerebellum and decreased H3R mRNA was found only in the medulla. In conjunction with the age-related decrease in hypocretin receptor 2 mRNA levels we have previously reported, decreased HA receptor mRNA levels may contribute to diminished alertness, sleep continuity, and diurnal rhythms of sleep and wakefulness in the aged.