Dysfunction of GABAergic neurons in the parafacial zone mediates sleep disturbances in a streptozotocin-induced rat model of sporadic Alzheimer's disease
Dysfunction of GABAergic neurons in the parafacial zone mediates sleep disturbances in a streptozotocin-induced rat model of sporadic Alzheimer's disease
复制标题
在链脲佐菌素诱导的散发性阿尔茨海默病大鼠模型中，面旁区 GABA 能神经元功能障碍介导睡眠障碍
DOI：
10.1007/s11011-017-0125-y
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发表时间：
2018-02-01
影响因子：
3.6
通讯作者：
Zhang, Yong-He
中科院分区：
文献类型：
--
作者：
Song, Jin-Zhi;Cui, Su-Ying;Zhang, Yong-He
睡眠障碍在阿尔茨海默病（AD）患者中普遍存在，并且通常先于痴呆的发作和进展。然而，目前还没有可靠的动物模型来研究散发性AD（sAD）患者的睡眠障碍，sAD占所有AD病例的90%以上。在本研究中，我们描述了睡眠/觉醒周期，并探讨了潜在的睡眠障碍的机制，在大鼠模型sAD诱导通过侧脑室注射链脲佐菌素（STZ）。STZ-icv大鼠表现出进行性减少慢波睡眠（SWS）在光相和整个光/暗周期开始从7天后STZ-icv。此外，从STZ-icv后14天开始观察到觉醒增加和快速眼动（REM）和非REM（NREM）睡眠减少。从第7天开始，STZ-icv大鼠在NREM睡眠期间表现出δ（0.5-4.0 Hz）功率的显著降低，伴随着β（12-30 Hz）和低γ频带（30-50 Hz）的功率增加，类似于在AD患者中观察到的睡眠质量缺陷。免疫组织化学染色显示，从STZ-icv后第7天开始，面旁区（PZ）c-Fos阳性GABA能神经元的比例显着降低。这些结果表明，STZ-icv大鼠模型是有用的，用于评估与AD相关的睡眠障碍，并暗示在PZ的GABA能神经元活动的失调与STZ诱导的睡眠障碍。
Sleep disturbances are prevalent among patients with Alzheimer's disease (AD) and often precede the onset and progression of dementia. However, there are no reliable animal models for investigating sleep disturbances in patients with sporadic AD (sAD), which accounts for more than 90% of all AD cases. In the present study, we characterize the sleep/wake cycles and explore a potential mechanism underlying sleep disturbance in a rat model of sAD induced via intracerebroventricular (icv) injection of streptozotocin (STZ). STZ-icv rats exhibited progressive decreases in slow wave sleep (SWS) during the light phase and throughout the light/dark cycle beginning from 7 days after STZ-icv. Additionally, increased wakefulness and decreased rapid-eye-movement (REM) and non-REM (NREM) sleep were observed from 14 days after STZ-icv. Beginning on day 7, STZ-icv rats exhibited significant decreases in delta (0.5-4.0 Hz) power accompanied by increased power in the beta (12-30 Hz) and low gamma bands (30-50 Hz) during NREM sleep, resembling deficits in sleep quality observed in patients with AD. Immunohistochemical staining revealed a significant reduction in the ratio of c-Fos-positive GABAergic neurons in the parafacial zone (PZ) beginning from day 7 after STZ-icv. These results suggest that the STZ-icv rat model is useful for evaluating sleep disturbances associated with AD, and implicate the dysregulation of GABAergic neuronal activity in the PZ is associated with sleep disturbance induced by STZ.