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

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

doi:10.3389/fncel.2023.1160761

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

Front Cell Neurosci. 2023 Jun 2:17:1160761. doi: 10.3389/fncel.2023.1160761. eCollection 2023.

Authors

Yun Li^#^{1

2}, Lina Zhao^#³, Kai Zhang^{1

2}, Mengxi Shen^{1

2}, Yize Li^{1

2}, Yang Yu^{1

2}, Jiafeng Yu^{1

2}, Jingyu Feng^{1

2}, Keliang Xie^{1

2

3}, Yonghao Yu^{1

2}

Affiliations

¹ Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.
² Tianjin Research Institute of Anesthesiology, Tianjin, China.
³ Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

^# Contributed equally.

Abstract

Post-operative sleep disturbance is a common feature of elderly surgical patients, and sleep fragmentation (SF) is closely related to post-operative 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 the 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 post-operative 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 post-operative SF on neurotransmitter metabolism and structural integrity of medial septum and hippocampal CA1 in aged C57BL/6J male mice. The animals received a 24-h SF procedure after isoflurane anesthesia and right carotid artery exposure surgery. 1H-MRS results showed after post-operative SF, the glutamate (Glu)/creatine (Cr) and glutamate + glutamine (Glx)/Cr ratios increased in the medial septum and hippocampal CA1, while the NAA/Cr ratio decreased in the hippocampal CA1. DTI results showed post-operative SF decreased the fractional anisotropy (FA) of white matter fibers in the hippocampal CA1, while the medial septum was not affected. Moreover, post-operative 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.

Keywords: 1H-MRS; CA1; DTI; aging; hippocampus; medial septum; post-operative sleep disturbance; sleep fragmentation.

Grants and funding

This research was supported by the National Natural Science Foundation of China (82001149, 82072150, and 82071243), the Scientific Research Project of Tianjin Municipal Education Commission (2022KJ232), the Tianjin Natural Science Foundation under the surface project (20JCYBJC00460), and the Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-036A).