Intranasal administration of orexin peptides: Mechanisms and therapeutic potential for age-related cognitive dysfunction.
Intranasal administration of orexin peptides: Mechanisms and therapeutic potential for age-related cognitive dysfunction.
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DOI：
10.1016/j.brainres.2018.08.024
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发表时间：
2020-03-15
期刊：
影响因子：
2.9
通讯作者：
Fadel JR
中科院分区：
文献类型：
--
作者：
Calva CB;Fadel JR
认知障碍是多种神经精神和神经系统疾病的核心特征，包括发作性睡病和年龄相关性痴呆。目前用于增强认知的药物治疗方法数量很少且疗效有限。因此，需要新的治疗策略。下丘脑食欲素（下丘脑分泌素）系统是生理功能的中央整合器，在调节认知方面发挥着重要作用。几种单和双食欲素受体拮抗剂可用于各种临床和临床前应用，但食欲素激动剂的缺乏限制了研究其治疗潜力的能力。为了克服这一障碍，人们正在研究直接鼻内施用食欲素肽作为认知功能障碍、嗜睡症或其他与食欲素信号传导缺陷有关的疾病的前瞻性治疗方法。在这里，我们描述了鼻内食欲素递送的可能机制和治疗潜力。结合鼻内食欲素-A给药可改善发作性睡病和睡眠剥夺受试者的认知功能的行为证据，我们对年轻和老年动物的神经化学研究强调了鼻内食欲素给药改善与年龄相关的神经传递缺陷的能力。总之，我们重点介绍我们实验室和其他实验室的先前和原创工作，这些工作为使用鼻内食欲素肽治疗认知功能障碍（特别是与年龄相关的认知障碍有关）提供了框架。
Cognitive impairment is a core feature of several neuropsychiatric and neurological disorders, including narcolepsy and age-related dementias. Current pharmacotherapeutic approaches to cognitive enhancement are few in number and limited in efficacy. Thus, novel treatment strategies are needed. The hypothalamic orexin (hypocretin) system, a central integrator of physiological function, plays an important role in modulating cognition. Several single- and dual-orexin receptor antagonists are available for various clinical and preclinical applications, but the paucity of orexin agonists has limited the ability to research their therapeutic potential. To circumvent this hurdle, direct intranasal administration of orexin peptides is being investigated as a prospective treatment for cognitive dysfunction, narcolepsy or other disorders in which deficient orexin signaling has been implicated. Here, we describe the possible mechanisms and therapeutic potential of intranasal orexin delivery. Combined with the behavioral evidence that intranasal orexin-A administration improves cognitive function in narcoleptic and sleep-deprived subjects, our neurochemical studies in young and aged animals highlights the capacity for intranasal orexin administration to improve age-related deficits in neurotransmission. In summary, we highlight prior and original work from our lab and from others that provides a framework for the use of intranasal orexin peptides in treating cognitive dysfunction, especially as it relates to age-related cognitive disorders.
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