Division of Respiratory Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No. 99, Wuhan, 430060, China.
Brain Res Bull. 2020 Nov;164:235-248. doi: 10.1016/j.brainresbull.2020.08.027. Epub 2020 Sep 6.
Cognitive impairment of obstructive sleep apnea syndrome (OSAS) patients is related to the basal forebrain (BF) cholinergic neurons. To further investigate the effect of the excitation or inhibition of BF cholinergic neurons on cognitive ability, we employed a chronic intermittent hypoxia (CIH) mice model and implanted microinjection cannulas in the BFs for targeted intervention, finally performed the behavioral experiments and examined immunohistochemistry and biochemical changes in the BFs. The results showed that (1) CIH induced cognitive decline in mice. (2) The excitation of BF cholinergic neurons attenuated cognitive decline, while the inhibition of these neurons aggravated cognitive impairment. (3) Microinjection of adenosine into the BF aggravated cognitive decline, while caffeine improved cognitive ability. (4) CIH induced BF cholinergic neuron injury in mice. (5) The excitation of BF cholinergic neurons alleviated cholinergic neuron injury, while the inhibition of these neurons aggravated this injury. (6) Microinjection of adenosine into the BF aggravated cholinergic neuron injury, while caffeine alleviated this injury. (7) CIH induced endoplasmic reticulum stress, oxidative stress and inflammatory responses in the BFs of mice. (8) The excitation of BF cholinergic neurons mitigated endoplasmic reticulum stress, oxidative stress and inflammatory responses in the BF in mice, while the inhibition of BF cholinergic neurons worsened these responses in the BF. (9) Microinjection of adenosine into the BF aggravated endoplasmic reticulum stress, oxidative stress and the inflammatory response, while caffeine alleviated these responses. This work indicates that CIH induces BF cholinergic neuron injury through multiple pathways, including endoplasmic reticulum stress, oxidative stress and the inflammatory response, thereby leading to cognitive dysfunction in mice. BF cholinergic neurons play a vital role in these pathways, thus reducing cholinergic neuron injury and restoring cognitive function in mice. Adenosine, which is an upstream modifier of acetylcholine, also plays an important role in altering cognitive ability.
阻塞性睡眠呼吸暂停综合征（OSAS）患者的认知障碍与基底前脑（BF）胆碱能神经元有关。为了进一步研究 BF 胆碱能神经元兴奋或抑制对认知能力的影响，我们采用慢性间歇性低氧（CIH）小鼠模型，在 BF 中植入微注射套管进行靶向干预，最后进行行为实验和 BF 中的免疫组织化学和生化变化检查。结果表明：（1）CIH 导致小鼠认知能力下降；（2）BF 胆碱能神经元兴奋可减轻认知能力下降，而抑制这些神经元则加重认知障碍；（3）将腺苷微注射到 BF 中会加重认知障碍，而咖啡因则改善认知能力；（4）CIH 诱导小鼠 BF 胆碱能神经元损伤；（5）BF 胆碱能神经元兴奋减轻胆碱能神经元损伤，而抑制这些神经元则加重损伤；（6）将腺苷微注射到 BF 中会加重胆碱能神经元损伤，而咖啡因则减轻损伤；（7）CIH 诱导小鼠 BF 内质网应激、氧化应激和炎症反应；（8）BF 胆碱能神经元兴奋减轻 BF 中内质网应激、氧化应激和炎症反应，而抑制 BF 胆碱能神经元则加重 BF 中的这些反应；（9）将腺苷微注射到 BF 中会加重内质网应激、氧化应激和炎症反应，而咖啡因则减轻这些反应。这项工作表明，CIH 通过多种途径诱导 BF 胆碱能神经元损伤，包括内质网应激、氧化应激和炎症反应，从而导致小鼠认知功能障碍。BF 胆碱能神经元在这些途径中起着至关重要的作用，从而减少胆碱能神经元损伤并恢复小鼠的认知功能。作为乙酰胆碱的上游调节剂，腺苷在改变认知能力方面也起着重要作用。
