Dopamine: The Essential Bridge Mediating Obstructive Sleep Apnea and Hippocampus‐Dependent Learning and Memory Impairments

Obstructive sleep apnea is a clinical syndrome that triggers a series of pathophysiologic changes, including disturbed sleep architecture, chronic intermittent hypoxia and hypercapnia, and ultimately severe cognitive dysfunction. The hippocampus plays a key role in various cognitive processes such as learning and memory. Previous studies have focused on inflammatory factors, oxidative stress, and apoptotic changes in the hippocampus. However, studies on neurotransmitter changes are scarce. Dopamine is an important neurotransmitter that has a direct effect on learning and memory formation in the hippocampus. This article summarizes the relationship between hippocampus-dependent learning and memory deficits induced by obstructive sleep apnea and dopamine, and explores how dopamine mediates hippocampus-dependent learning and memory deficits associated with obstructive sleep apnea. Detailed searches were performed by utilizing open-ended keywords on PubMed and manually searching the reference lists of the identified articles; all references up to December 31, 2024, were used. Search terms included "obstructive sleep apnea," "OSA," "chronic intermittent hypoxia," "sleep fragmentation," "sleep deprivation," "sleep disorder," "apoptosis," "inflammation," "oxidative stress," "hippocampus," and "dopamine." The final article includes all articles that explicitly address dopamine maintenance of memory and how obstructive sleep apnea affects hippocampal dopamine. First, obstructive sleep apnea inhibits hippocampal dopamine synthesis. Second, downregulated dopamine induces hippocampus-associated inflammatory responses, oxidative stress, and apoptosis. Finally, intermittent hypoxia may also further exacerbate dopamine deficiency by inducing a positive cycle of dopamine downregulation. The net effect of these processes is a hippocampus-dependent decline in learning and memory capacity, which is characteristic of obstructive sleep apnea. Dopamine plays a crucial role in obstructive sleep apnea-associated hippocampus-dependent learning and memory deficits, not only due to the neural signaling role of dopamine itself, but also due to obstructive sleep apnea-associated inflammation, apoptosis, and oxidative stress, which are also closely related to dopamine.