Intranasal administration of orexin peptides: Mechanisms and therapeutic potential for age-related cognitive dysfunction.

Brain Research
Coleman B Calva, Jim R Fadel

Abstract

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 adm...Continue Reading

Citations

May 28, 2019·Scientific Reports·Trevor StewardFernando Fernández-Aranda
Jun 11, 2020·Psychiatry Investigation·Yoo Hyun Um, Hyun Kook Lim
Oct 10, 2020·Brain Circulation·Hayder M Al-KuraishyAli I Al-Gareeb
Oct 19, 2020·Genes, Brain, and Behavior·Archana Durairaja, Markus Fendt
Feb 24, 2021·Physiology & Behavior·Jennifer M ErichsenJim R Fadel
Jun 20, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jacqueline B MehrMorgan H James
Jan 20, 2022·Journal of Internal Medicine·Laura H JacobsonLuis de Lecea

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