Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065;
Department of Neurology, Icahn School of Medicine, Mount Sinai, New York, NY 10029.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10250-10255. doi: 10.1073/pnas.1700177114. Epub 2017 Sep 5.
Sleep-disordered breathing (SDB) is a common disorder in aging that is associated with cognitive decline, including significant executive dysfunction, for which the neurobiological underpinnings remain poorly understood. Using proton magnetic resonance spectroscopy (1H MRS), this study assessed whether dysregulation of the homeostatic balance of the major inhibitory and excitatory amino acid neurotransmitter systems of γ-aminobutyric acid (GABA) and glutamate, respectively, play a role in SDB. Levels of GABA and those of the combined resonances of glutamate and glutamine (Glx), were measured by 1H MRS in the left dorsolateral prefrontal cortex (l-DLPFC) and bilateral hippocampal regions of 19 older adults (age ± SD: 66.1 ± 1.9 years) with moderate to severe SDB, defined as having an Apnea-Hypopnea Index (AHI) greater than 15 as assessed by polysomnography, and in 14 older adults (age ± SD: 62.3 ± 1.3 years) without SDB (AHI < 5). In subjects with SDB, levels of l-DLPFC GABA, but not Glx, were significantly lower than in control subjects ( < 0.0002). Additionally, there was a negative correlation between l-DLPFC GABA levels, but not Glx, and SDB severity by AHI ( = -0.68, < 0.0001), and a positive correlation between l-DLPFC GABA levels, but not Glx, and minimal oxygen saturation during sleep ( = 0.62, = 0.0005). By contrast, no group differences or oxygenation associations were found for levels of GABA or Glx in right or left hippocampal region. These findings are interpreted in terms of a pathophysiological model of SDB in which hypoxia-mediated inhibitory neurotransmission deficit in DLPFC could lead to hyperexcitability and, potentially neuronal dysfunction and cognitive decline.
睡眠呼吸障碍（SDB）是衰老过程中的一种常见疾病，与认知能力下降有关，包括严重的执行功能障碍，其神经生物学基础仍知之甚少。本研究使用质子磁共振波谱（1H MRS）评估主要抑制性和兴奋性氨基酸神经递质系统γ-氨基丁酸（GABA）和谷氨酸的内稳态平衡失调是否在 SDB 中起作用。通过 1H MRS 在 19 名年龄较大（年龄±标准差：66.1±1.9 岁）患有中度至重度 SDB（定义为通过多导睡眠图评估的呼吸暂停-低通气指数（AHI）大于 15）的个体的左侧背外侧前额叶皮层（l-DLPFC）和双侧海马区以及 14 名年龄较大（年龄±标准差：62.3±1.3 岁）无 SDB（AHI < 5）的个体中测量 GABA 和谷氨酸和谷氨酰胺（Glx）的联合共振的水平。在 SDB 患者中，l-DLPFC GABA 的水平显著低于对照组（<0.0002）。此外，l-DLPFC GABA 水平与 SDB 严重程度（通过 AHI 评估）呈负相关（= -0.68，<0.0001），而 l-DLPFC GABA 水平与睡眠期间最小血氧饱和度呈正相关（= 0.62，= 0.0005）。相比之下，在右侧或左侧海马区未发现 GABA 或 Glx 水平的组间差异或与氧合作用的关联。这些发现是根据 SDB 的病理生理学模型来解释的，在该模型中，DLPFC 中的缺氧介导的抑制性神经传递缺陷可导致过度兴奋，并可能导致神经元功能障碍和认知能力下降。
