Alterations in hippocampal somatostatin interneurons, GABAergic metabolism, and ASL perfusion in an aged male mouse model of POCD aggravated by sleep fragmentation

• Published in: Physiological reports Vol. 12; no. 23; pp. e70153 - n/a
• Main Authors: Li, Yun, Yu, Jiafeng, Yang, Ningzhi, Long, Siwen, Li, Yize, Zhao, Lina, Yu, Yonghao
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.12.2024; John Wiley and Sons Inc; Wiley
• Subjects: Aging; Aging - metabolism; Anesthesia; Animal cognition; Animals; Blood flow; Brain research; Carotid arteries; Cerebral blood flow; Cerebrovascular Circulation; Cognitive ability; Disease Models, Animal; gamma-Aminobutyric Acid - metabolism; Glutamate decarboxylase; Glutamate Decarboxylase - metabolism; Glutamic acid transporter; Hippocampus; Hippocampus - metabolism; Immunofluorescence; Interneurons; Interneurons - metabolism; Laboratory animals; magnetic resonance imaging; Male; Maze Learning; Memory; Metabolism; Mice; Mice, Inbred C57BL; Neuropeptide Y; Neuropeptide Y - metabolism; Original; Pattern recognition; Perfusion; POCD; Post traumatic stress disorder; Postoperative Cognitive Complications - etiology; Postoperative Cognitive Complications - metabolism; Regular Manuscript; Sleep; Sleep apnea; Sleep deprivation; Sleep Deprivation - metabolism; Sleep Deprivation - physiopathology; sleep fragmentation; Somatostatin; Somatostatin - metabolism; Spatial memory; Spin labeling; Spin Labels; Surgery; Vesicular Inhibitory Amino Acid Transport Proteins - metabolism; γ-Aminobutyric acid; Beijing China; China; magnetic resonance imaging; aging; hippocampus; POCD; sleep fragmentation; somatostatin
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.70153

Sleep fragmentation (SF) is increasingly recognized as a contributing factor to postoperative cognitive dysfunction (POCD). Given the critical roles of somatostatin (SST) interneurons, associated gamma‐aminobutyric acid (GABA)ergic neurotransmitters, and hippocampal perfusion in sleep‐related cognition, this study examined changes in these mechanisms in preoperative SF affecting POCD induced by anesthesia/surgery in aged male mice. The Morris water maze (MWM), novel object recognition (NOR), and Y maze tests were utilized to evaluate POCD. Arterial spin labeling (ASL) was employed to measure hippocampal regional cerebral blood flow (rCBF). In vitro assays quantified the levels of GABAergic metabolites—such as SST, neuropeptide Y (NPY), glutamic acid decarboxylase 1 (GAD1), vesicular GABA transporter (VGAT), and GABA and the distribution of SST interneurons in the hippocampus through enzyme‐linked immunosorbent assay and immunofluorescence. Preoperative 24‐h SF exacerbated anesthesia/surgery‐induced spatial memory impairments observed in the MWM, NOR, and Y maze tests. Preoperative 24‐h SF significantly increased the number of SST interneurons in hippocampal CA1, elevated hippocampal levels of SST, NPY, GAD1, and GABA, and reduced the rCBF. Preoperative SF aggravated POCD in aged male mice, with an increased number of SST interneurons in hippocampal CA1, elevated hippocampal GABAergic metabolites, and a further reduction in rCBF. Preoperative 24‐h sleep fragmentation aggravates anesthesia/surgery‐induced POCD in aged mice, accompanied by an increase in the number of SST interneurons in the hippocampal CA1 region, an increase in the levels of hippocampal SST, NPY, GAD1, and GABA, and a decrease in hippocampal ASL perfusion, as well as hippocampal neuron damage.