Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, United States; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, United States; Pharmacology Graduate Program, Weill Cornell Medicine, New York, NY, United States.
Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, United States; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, United States.
Int Rev Neurobiol. 2023;170:121-154. doi: 10.1016/bs.irn.2023.04.006. Epub 2023 May 5.
Adenosine A receptors have been studied extensively in the context of motor function and movement disorders such as Parkinson's disease. In addition to these roles, A receptors have also been increasingly implicated in cognitive function and cognitive impairments in diverse conditions, including Alzheimer's disease, schizophrenia, acute brain injury, and stress. We review the roles of A receptors in cognitive processes in health and disease, focusing primarily on the effects of reducing or enhancing A expression levels or activities in animal models. Studies reveal that A receptors in neurons and astrocytes modulate multiple aspects of cognitive function, including memory and motivation. Converging evidence also indicates that A receptor levels and activities are aberrantly increased in aging, acute brain injury, and chronic disorders, and these increases contribute to neurocognitive impairments. Therapeutically targeting A receptors with selective modulators may alleviate cognitive deficits in diverse neurological and neuropsychiatric conditions. Further research on the exact neural mechanisms of these effects as well as the efficacy of selective A modulators on cognitive alterations in humans are important areas for future investigation.
腺苷 A 受体在运动功能和运动障碍(如帕金森病)的背景下得到了广泛研究。除了这些作用外,A 受体也越来越多地与认知功能和多种情况下的认知障碍有关,包括阿尔茨海默病、精神分裂症、急性脑损伤和应激。我们回顾了 A 受体在健康和疾病中的认知过程中的作用,主要关注在动物模型中降低或增强 A 表达水平或活性的影响。研究表明,神经元和星形胶质细胞中的 A 受体调节认知功能的多个方面,包括记忆和动机。越来越多的证据还表明,A 受体水平和活性在衰老、急性脑损伤和慢性疾病中异常升高,这些升高导致神经认知障碍。用选择性调节剂靶向 A 受体可能会减轻多种神经和神经精神疾病中的认知缺陷。进一步研究这些影响的确切神经机制以及选择性 A 调节剂对人类认知改变的疗效是未来研究的重要领域。