3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress,Metabolic Brain Disease

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3-Methyladenine ameliorates surgery-induced anxiety-like behaviors in aged mice by inhibiting autophagy-induced excessive oxidative stress
Metabolic Brain Disease ( IF 3.2 ) Pub Date : 2023-04-25 , DOI: 10.1007/s11011-023-01217-3
Song-Tao Wu ₁ , Shan-Shan Han ₁ , Xi-Ming Xu ₁ , Hai-Jun Sun ₁ , Hua Zhou ₂ , Kun Shang ₂ , Zi-Hao Liu ₂ , Shu-Juan Liang ₁

Affiliation

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.

中文翻译：

3-甲基腺嘌呤通过抑制自噬引起的过度氧化应激改善老年小鼠手术引起的焦虑样行为

背景

术后焦虑是老年患者常见的手术并发症。最近的研究发现过度自噬与包括焦虑在内的多种神经系统疾病有关。本研究旨在确定 3-甲基腺嘌呤 (3-MA) 给药是否可以减少腹部剖腹探查术后小鼠模型的焦虑样行为。

方法

使用20月龄雄性C57BL/6小鼠建立腹部剖腹探查术后焦虑模型。手术后立即通过脑室内注射 3-MA（6、30 和 150 mg/ml）。手术后 14 天，使用大理石埋藏、高架十字迷宫测试和杏仁核局部场电位记录对小鼠进行评估。NeuN 阳性细胞中磷酸化 Akt、Beclin-1、LC3B、核因子红细胞 2 相关因子 2 (Nrf2) 占据区域的表达水平、超氧化物歧化酶 (SOD) 活性、丙二醛 (MDA) 和谷胱甘肽 ( GSH）在手术后24小时进行测量。

结果

腹部探查剖腹手术14天后，注射3-MA逆转了埋藏的弹珠数量增加，减少了张臂时间，并增强了θ振荡功率。此外，施用 3-MA 降低了磷酸化 Akt 与总 Akt 的比率，降低了 Beclin-1 和 LC3B 的表达，降低了 MDA 水平，并增加了 NeuN 阳性细胞中 Nrf2 占据区域的比率、SOD 活性、和腹部剖腹探查条件下的 GSH 水平。