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Increased brain histamine H 3 receptor expression during hibernation in golden-mantled ground squirrels

机译:黄金地松鼠冬眠期间脑组胺H 3受体表达增加

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Background Hibernation 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. Results In 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. Conclusions These 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.
机译:背景技术冬眠是一种生理功能大大降低和CNS活性严重降低的状态。先前我们已经证明,冬眠期间大脑中的组胺水平升高,组胺与其第一代谢产物之间的比例也升高,这表明在此状态下组胺的周转率增加。抑制性组胺H 3 受体同时具有自体和异体受体功能,使其最有可能在冬眠期间参与调节组胺以及其他神经递质的活性。考虑到越来越多的证据表明,在冬眠期间转录和翻译的总体下降,除少数对这种生理状况重要的蛋白质外,我们认为组胺H 3 受体表达增加清楚地表明该受体具有重要的休眠相关功能。结果在这项研究中,我们显示,通过原位杂交,冬眠期间皮层,尾状核和壳状核中的组胺H 3 受体mRNA升高,并且该升高伴随着大脑皮层中受体结合的升高,苍白球和黑质。这些结果表明,在皮质神经元以及纹状体外层和纹状体GABA能神经元中H 3 受体的表达与冬眠相关。 GTP-γ-S结合放射自显影显示,在整个冬眠周期中,组胺均可刺激苍白球和黑质中的H 3 受体,这表明它们在冬眠期间具有功能活性。结论这些结果表明,组胺H 3 受体基因是少数在冬眠期间具有增加的转录物的基因之一,表明该受体在调节这种状态中具有重要作用。此外,该受体在基底神经节中具有功能活性,提示其在调节例如神经节的功能。冬眠期间的多巴胺能传播。

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