Effects of the excitation or inhibition of basal forebrain cholinergic neurons on cognitive ability in mice exposed to chronic intermittent hypoxia

Abstract

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.