AUTHOR=Li Yun , Zhao Lina , Zhang Kai , Shen Mengxi , Li Yize , Yu Yang , Yu Jiafeng , Feng Jingyu , Xie Keliang , Yu Yonghao 

TITLE=Neurometabolic and structural alterations of medial septum and hippocampal CA1 in a model of post-operative sleep fragmentation in aged mice: a study combining 1H-MRS and DTI

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1160761

DOI=10.3389/fncel.2023.1160761

ISSN=1662-5102

ABSTRACT=Postoperative sleep disturbance is a common feature of elderly surgical patients, and sleep fragmentation (SF) phenotype is closely related to postoperative cognitive dysfunction (POCD). SF is characterized by sleep interruption, increased number of awakenings and sleep structure destruction, similar to obstructive sleep apnea (OSA). Research shows that sleep interruption can change neurotransmitter metabolism and structural connectivity in sleep and cognitive brain regions, of which medial septum and hippocampal CA1 are key brain regions connecting sleep and cognitive processes. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method for the evaluation of neurometabolic abnormalities. Diffusion tensor imaging (DTI) realizes the observation of structural integrity and connectivity of brain regions of interest in vivo. However, it is unclear whether postoperative SF induces harmful changes in neurotransmitters and structures of the key brain regions and their contribution to POCD. In this study, we evaluated the effects of postoperative SF on neurotransmitter metabolism and structural integrity of medial septal nucleus and hippocampal CA1 in aged C57BL/6J male mice. The animals received a 24-hour SF procedure after isoflurane anesthesia and right carotid artery exposure surgery. 1H-MRS results showed after postoperative SF, increases in glutamate (Glu)/creatine (Cr), glutamate + glutamine (Glx)/Cr and N-acetylaspartate (NAA)/Cr of medial septum, while decrease in NAA/Cr of hippocampal CA1 region. DTI results showed postoperative SF decreased the anisotropy fraction (FA) of white matter fibers in hippocampal CA1 region, while the medial septum was not affected. Moreover, postoperative SF aggravated subsequent Y-maze and novel object recognition performances accompanied by abnormal enhancement of glutamatergic metabolism signal. This study suggests that 24-h SF induces hyperglutamate metabolism level and microstructural connectivity damage in sleep and cognitive brain regions in aged mice, which may be involved in the pathophysiological process of POCD.