呼吸中枢化学反应性、发作性睡病与HLA-DQB1*0602基因

呼吸中枢低氧反应性的高低受遗传的调控,尽管动物实验发现了多个候选基因,但目前尚未见人体相关基因的报告.发作性睡病(narcolepsy)是一种少见睡眠疾病,以难以控制的嗜睡、发作性猝倒、睡瘫、入睡幻觉及夜间睡眠紊乱为主要临床特点,超过95%的典型患者存在人类白细胞抗原(HLA)DQB1*0602基因阳性、脑脊液下丘脑分泌素降低或消失等表现.患者常合并睡眠呼吸暂停,动物实验结果显示下丘脑分泌素缺乏可导致清醒状态下的呼吸中枢高CO2反应性降低,提示发作性睡病患者存在呼吸调节功能缺陷.     

Activation of immobility-related hippocampal theta by cholinergic septohippocampal neurons during vestibular stimulation

The vestibular system has been suggested to participate in spatial navigation, a function ascribed to the hippocampus. Vestibular stimulation during spatial navigation activates a hippocampal theta rhythm (4-10 Hz), which may enhance spatial processing and motor response. We hypothesize that a cholinergic, atropine-sensitive theta is generated during passive whole-body rotation in freely behaving rats. Hippocampal EEGs were recorded by implanted electrodes in CA1 while rats were rotated on a vertical axis, for a minute or longer, at different angular velocities. Rotation induced a continuous hippocampal theta rhythm while the rat was immobile, in both light and dark conditions. Theta peak frequency showed a significant increase during high (50-70 rpm) as compared with a lower (20-49 rpm) rotational velocity. Rotation-induced theta was abolished by muscarinic receptor antagonist atropine sulfate (50 mg/kg i.p.) but not by atropine methyl nitrate (50 mg/kg i.p.), which did not pass the blood-brain barrier. Theta was attenuated in rats in which cholinergic neurons in the medial septum (MS) were lesioned with 192 IgG-saporin (0.14 μg in 0.4 μl), as confirmed by depletion of MS cells immunoreactive to choline acetyltransferase and an absence of acetylcholinesterase staining in the hippocampus. Bilateral lesion of the vestibular receptors by sodium arsanilate (30 mg in 0.1 ml, intratympanically) also attenuated the rotation-induced theta rhythm. In intact rats, field excitatory postsynaptic potentials (fEPSPs) in CA1 evoked by commissural stimulation were smaller during walking or rotation as compared with during immobility. Modulation of fEPSP was absent following atropine sulfate in intact rats and in 192 IgG-saporin lesion rats. In summary, this is the first report of a continuous atropine-sensitive hippocampal theta in the rat induced by vestibular stimulation during rotation, and accompanied by cholinergic modulation of hippocampal synaptic transmission. Vestibular-activated septohippocampal cholinergic activity could be an important component in sensorimotor processing and spatial memory.     

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