[Orexinergic neurons and noradrenergic awakening system in general anesthesia].
[Orexinergic neurons and noradrenergic awakening system in general anesthesia].
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发表时间：
2007
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通讯作者：
K. Hirota
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作者：
K. Hirota
睡眠-觉醒周期由单胺能、胆碱能和GABA能神经元活动之间的相互作用调节。单胺能神经元包括去甲肾上腺素能神经元（蓝斑）、组胺能神经元（结节乳头核）和多巴胺能神经元（中缝核），它们广泛投射到大脑皮层、丘脑和脑干，是睡眠调节的中枢。有趣的是，虽然显示前原食欲素（前原-OX）免疫反应性的细胞体仅限于下丘脑，但OX能神经元密集地投射到LC、结节乳头核和中缝核。这些证据表明单胺能和OX能神经元之间的联系。我们发现，OXA和B引起大鼠大脑皮层片去甲肾上腺素的释放，但组胺和5-羟色胺的释放没有引起。去甲肾上腺素能神经投射到皮质的神经元均来自LC。因此，大脑皮层中的去甲肾上腺素能神经元可能是OX能神经元和单胺能神经元之间的主要联系。因此，我们研究了OXergic-noradrenergic神经元和麻醉。我们发现，OXs减少麻醉时间，这是由SB 334867（OX 1受体拮抗剂）逆转。然而，由于α 2-受体配体不影响大脑皮层切片的OX-去甲肾上腺素释放，因此α 2-受体可能不参与大脑皮层中的OX-去甲肾上腺素能神经元。荷包牡丹碱（GABAA受体拮抗剂）不能逆转巴比妥类药物对OX-去甲肾上腺素释放的抑制作用，但能显著逆转K+诱发的释放。此外，蝇蕈醇（GABAA受体激动剂）不抑制OX-去甲肾上腺素释放，但抑制K+诱发的释放。因此，GABAA受体也可能不参与。
The sleep-wake cycle is regulated by interaction between monoaminergic, cholinergic and GABAergic neuronal activities. Monoaminergic neurons including noradrenergic (locus coeruleus: LC), histaminergic (tuberomammillary nucleus) and serotonergic (raphe nuclei) neurons projected diffusely to the cerebrocortex, thalamus and brainstem are known as the center of sleep regulation. Interestingly, although the cell bodies displaying prepro-orexin (prepro-OX) immunoreactivity are limited to the hypothalamus, OXergic neurons densely project to LC, tuberomammillary nucleus and raphe nuclei. These evidences suggest a link between monoaminergic and OXergic neurons. We found that OXA and B evoke norepinephrine release from rat cerebrocortical slices but histamine and serotonin releases are not evoked. All noradrenergic projections to cerebrocortex originate from the LC. Thus, the main link between OXergic and monoaminergic neurons may be noradrenergic in the cerebral cortex. Therefore, we have studied OXergic-noradrenergic neurons and anesthesia. We found that OXs reduced anesthesia time, which was reversed by SB334867 (OX1-receptor antagonist). However, as alpha2-receptor ligands did not affect OXs-norepinephrine release from cerebrocortical slices, alpha2-receptors may not be involved in OXergic-noradrenergic neurons in the cerebral cortex. Bicuculline (GABAA-receptor antagonist) could not reverse inhibitory effects of barbiturates on OXs-norepinephrine release but significantly reversed these effects on K+-evoked release. Moreover, muscimol (GABAA-receptor agonist) did not inhibit the OX-norepinephrine release but inhibited the K+-evoked release. Therefore, GABAA-receptor may also not be involved.