Studies of neurophysiological regulation of sleep-wake states using animal models for sleep research

近几十年来，许多参与睡眠-觉醒调节的化学和神经元底物已经被识别出来。最近，食欲素A和B参与了进食和觉醒状态的调节，被发现。脑室注射食欲素A和食欲素B可引起大鼠的觉醒效应。在本研究中，我们研究了体液因素在睡眠-觉醒状态的神经生理调节中的作用以及用于睡眠研究的动物模型。脑室注射食欲素A 5小时后，觉醒时间显著增加，高于基线值。OX2R拮抗剂可降低增食欲素A诱导的觉醒。OX2R拮抗剂单独治疗对各睡眠参数均有轻微影响，但差异无统计学意义。预先给予OX2R拮抗剂可显著抑制增食欲素A诱导的大鼠觉醒。因此，这项研究表明，OX2R参与了觉醒状态的调节。众所周知，胃动素可以调节摄食系统。我们观察了侧脑室注射胃动素(1，10，50,100nml)对自由活动大鼠睡眠-觉醒周期的影响。100nmoL的胃动素显著增加觉醒次数，较基线增加75.0%(p&lt；0.05)。这些发现表明，胃动素也调节睡眠-觉醒状态和行为反应。帕金森病(PD)是一种进行性神经退行性疾病，黑质致密部多巴胺能神经元(SNPC)被破坏。在这项研究中，α-突触核蛋白转基因(TG)小鼠被用来研究睡眠结构，并与野生型(WT)小鼠进行比较。Tg和WT小鼠的睡眠结构分析没有显著差异。为了验证观察到的睡眠-觉醒周期扰动，需要利用PD模型进一步研究多巴胺能系统对睡眠-觉醒周期的影响。

In recent decades, many of the chemical and neuronal substrates involved in sleep-wake regulation have been identified. Recently, orexins A and B involved in the regulation of the feeding and arousal states, were identified. An intracerebroventricular (icv) infusion of both orexins A and B has been observed to induce arousal effects in rats. In the present studies, we investigated the involvement of humoral factors in neurophysiological regulation of sleep-wake states and animal models for sleep research.1. An icv infusion of orexin A for a 5-h period markedly increased the amount of wakefulness over the baseline value. OX2R antagonist decreased orexin A-induced wakefulness. Although OX2R antagonist treatment alone slightly changed each sleep parameter, no significant difference was observed. Pretreatment with OX2R antagonist, significant inhibited orexin A-induced wakefulness in rats. The finding this study therefore suggest that OX2R involved in arousal state regulation.2. Motilin is known to regulate the feeding system. We investigated the effects of icv infusion of motilin (1, 10, 50, 100 nml) on the sleep-waking cycle in the freely behaving rats. Motilin at the dose of 100 nmol markedly increased the amount of wakefulness by 75.0% (p<0.05) over the baseline value. These finding suggest that motilin also modulates sleep-wake states and behavioral responses.3. Parkinson's Disease (PD) is a progressive neurodegenerative disease wherein dopaminergic neuron in the substantia nigra pars compacta (SNpc) are destroyed. In this study, α-synuclein transgenic (TG) mice for the diminished expression of dopaminergic neurons in SNpc were used to investigate sleep architecture, and compared to wild type (WT) mice. Analysis of sleep architecture had no significant differences between TG and WT mice. Further research on the influence of the dopaminergic system on the sleep-wake cycle using PD models is needed to validate the observed sleep-wake cycle disturbances.