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

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

Abstract 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‐relat...

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Main Authors: Yun Li, Jiafeng Yu, Ningzhi Yang, Siwen Long, Yize Li, Lina Zhao, Yonghao Yu
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Physiological Reports
Subjects:
aging
hippocampus
magnetic resonance imaging
POCD
sleep fragmentation
somatostatin
Online Access:https://doi.org/10.14814/phy2.70153
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Summary:Abstract 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.
ISSN:2051-817X

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