Abstract
Background
Postoperative anxiety is a common surgical complication in older patients. Research has recently linked excessive autophagy to several neurological disorders, including anxiety. This study aimed to determine whether 3-Methyladenine (3-MA) administration reduced anxiety-like behaviors in a mouse model following abdominal exploratory laparotomy.
Methods
An abdominal exploratory laparotomy model of postoperative anxiety was established using male C57BL/6 mice aged 20 months. 3-MA (6, 30, and 150 mg/ml) was administered via intracerebroventricular immediately following surgery. The mice were assessed 14 days after surgery using the marble burying, elevated plus maze tests, and local field potential recording in the amygdala. The levels of expression of phosphorylated-Akt, Beclin-1, LC3B, nuclear factor erythroid 2-related factor 2 (Nrf2)-occupied regions in NeuN-positive cells, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and glutathione (GSH) were measured at 24 h after surgery.
Results
The injection of 3-MA reversed the increased number of marbles buried, decreased time spent in the open arm, and enhanced θ oscillation power after 14 days of abdominal exploratory laparotomy. In addition, administration of 3-MA reduced the ratio of phosphorylated- to total-Akt, decreased expression in Beclin-1 and LC3B, attenuated MDA levels, and increased the ratio of Nrf2-occupied areas in NeuN-positive cells, SOD activity, and GSH levels under abdominal exploratory laparotomy conditions.
Conclusions
3-MA improved anxiety-like behaviors in aged mice undergoing abdominal exploratory laparotomy by inhibiting excessive autophagy-induced oxidative stress. These results suggest that 3-MA could be an effective treatment for postoperative anxiety.
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Data Availability
All data generated and analyzed during this study are included in this published article and its supplementary information file.
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This study was supported by the key research and development program from the Bureau of Science and Technology of Qinhuangdao (202101A186).
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Song-Tao Wu: Methodology, Investigation, Formal Analysis, Writing - Original Draft. Shan-Shan Han: Methodology, Formal Analysis, Data Curation. Xi-Ming Xu: Methodology, Formal Analysis, Software. Hai-Jun Sun: Methodology, Formal Analysis. Hua Zhou: Investigation, Formal Analysis. Kun Shang: Methodology, Software. Zi-Hao Liu: Methodology, Formal Analysis. Shu-Juan Liang: Conceptualization, Writing - Review & Editing, Supervision, Project Administration.
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All animal studies were carried out under the National Institute of Health’s Guideline for the Care and Use of Laboratory Animals. The Animal Review Board also approved the protocols involving animals of the First Hospital of Qinhuangdao (2021Q085).
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Wu, ST., Han, SS., Xu, XM. et al. 3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress. Metab Brain Dis 38, 1913–1923 (2023). https://doi.org/10.1007/s11011-023-01217-3
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DOI: https://doi.org/10.1007/s11011-023-01217-3