Calva Coleman B, Fayyaz Habiba, Fadel Jim R
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC, United States.
Front Aging Neurosci. 2020 Jan 22;11:362. doi: 10.3389/fnagi.2019.00362. eCollection 2019.
Cognitive function represents a key determinative factor for independent functioning among the elderly, especially among those with age-related cognitive disorders. However; existing pharmacotherapeutic tactics for treating these disorders provide only modest benefits on cognition. The hypothalamic orexin (hypocretin) system is uniquely positioned, anatomically and functionally, to integrate physiological functions that support proper cognition. The ongoing paucity of orexin receptor agonists has mired the ability to study their potential as cognitive enhancers. Fortunately, intranasal administration of native orexin peptides circumvents this issue and others concerning peptide transport into the central nervous system (CNS). To investigate the ability of intranasal orexin-A (OxA) administration to improve the anatomical, neurochemical, and behavioral substrates of age-related cognitive dysfunction, these studies utilized a rodent model of aging combined with acute intranasal administration of saline or OxA. Here, intranasal OxA increases c-Fos expression in several telencephalic brain regions that mediate important cognitive functions, increases prefrontal cortical acetylcholine efflux, and alters set-shifting-mediated attentional function in rats. Ultimately, these studies provide a framework for the possible mechanisms and therapeutic potential of intranasal OxA in treating age-related cognitive dysfunction.
认知功能是老年人独立生活能力的关键决定因素，尤其是在那些患有与年龄相关认知障碍的人群中。然而，现有的治疗这些障碍的药物治疗策略对认知的改善作用有限。下丘脑食欲素（促食欲素）系统在解剖学和功能上具有独特的地位，能够整合支持正常认知的生理功能。目前食欲素受体激动剂的匮乏阻碍了对其作为认知增强剂潜力的研究。幸运的是，经鼻给予天然食欲素肽可避免这一问题以及其他有关肽转运至中枢神经系统（CNS）的问题。为了研究经鼻给予食欲素-A（OxA）改善与年龄相关认知功能障碍的解剖学、神经化学和行为学基础的能力，这些研究采用了衰老啮齿动物模型，并结合经鼻急性给予生理盐水或OxA。在此，经鼻给予OxA可增加在几个介导重要认知功能的端脑区域中的c-Fos表达，增加前额叶皮质乙酰胆碱外流，并改变大鼠的转换介导的注意力功能。最终，这些研究为经鼻给予OxA治疗与年龄相关认知功能障碍的可能机制和治疗潜力提供了一个框架。
