Development of a novel gene therapy on narcolepsy using AAV vectors and artificial GPCRs

人类食欲素神经元的丧失与发作性睡病有关，发作性睡病是一种以白天过度嗜睡和突然发作为特征的睡眠障碍。然而，确切的神经机制的食欲素神经元下游仍然未知。我们发现，蓝斑去甲肾上腺素能和中缝背核神经元发挥不同的作用，在调节睡眠/觉醒的食欲素神经元：前者稳定清醒发作（减少嗜睡），后者抑制cataerosis小鼠。此外，我们开发了一种系统，通过使用重组AAV载体和称为DREADD的人工GPCR人工激活这些神经元来抑制小鼠中的嗜睡症。

The loss of orexin neurons in humans is associated with narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. However, the precise neural mechanisms downstream of orexin neurons remain unknown.We found that the locus coeruleus noradrenergic and dorsal raphe serotonergic neurons play differential roles in the regulation of sleep/wakefulness by orexin neurons: the former stabilizes wakefulness episodes (reduce sleepiness) and the latter suppresses cataplexy in mice. In addition, we developed a system to suppress narcolepsy in mice by artificially activating these neurons using recombinant AAV vectors and an artificial GPCR called DREADD.