Terao Akira, Steininger Teresa L, Morairty Stephen R, Kilduff Thomas S
Molecular Neurobiology Laboratory, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
Neurosci Lett. 2004 Jan 23;355(1-2):81-4. doi: 10.1016/j.neulet.2003.10.061.
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.
多条证据表明，组胺能（HA）系统对清醒和行为状态调节很重要。我们研究了一个假说，即HA系统会发生与年龄相关的变化，这可能与衰老过程中警觉性下降有关。虽然在C57BL/6小鼠中，组氨酸脱羧酶mRNA水平不会随年龄变化，但在几个脑区的组胺H1受体（H1R）、组胺H2受体（H2R）和组胺H3受体（H3R）mRNA水平上发现了显著差异。在H1R mRNA中观察到最广泛的变化，相对于3月龄动物，24月龄小鼠的皮质、下丘脑、海马体和延髓中的H1R mRNA显著降低（27%-38%）。H2R mRNA水平与年龄相关的变化仅限于脑桥和小脑，而H3R mRNA水平降低仅在延髓中发现。结合我们之前报道的与年龄相关的下丘脑分泌素受体2 mRNA水平下降，HA受体mRNA水平下降可能导致老年人警觉性降低、睡眠连续性变差以及睡眠和清醒的昼夜节律紊乱。
