The mechanism of PTGES3/HSP90 in the medial prefrontal cortex regulating obesity-related cognitive impairment
10.19405/j.cnki.issn1000-1492.2025.04.002
- Author:
Jinyan Wang
1
;
Jia Hu
1
;
Rui Hu
1
;
Chunxia Huang
1
;
Qi Xue
1
Author Information
1. Dept of Anesthesiology and Perioperative Medicine，The Second Affiliated Hospital of Anhui Medical University， Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes，Hefei 230601
- Publication Type:Journal Article
- Keywords:
PTGES3;
HSP90;
obesity;
cognition disfunction;
neuroinflammation
- From:
Acta Universitatis Medicinalis Anhui
2025;60(4):596-603
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the mechanism of prostaglandin E synthase 3(PTGES3)/heat shock protein 90(HSP90) in the medial prefrontal cortex regulating obesity-related cognitive dysfunction.
Methods: This study consisted of clinical trials and animal experiments. In part one, obese patients scheduled for bariatric surgery, and healthy adults matching gender and age were recruited at the same time to reach 10 cases in each group. The cognitive level was assessed with trail making test part A(TMT-A) and victoria stroop tests(VST). Four-dimensional data-independent acquisition(4D-DIA) was used to screen the proteome changes in peripheral blood. In part two, forty SPF healthy male C57BL/6J mice were randomly divided into four groups: normal diet group(ND group), high fat diet induced obesity group(DIO group), DIO supplemented with the control virus group(DIO+Scramble group) and DIO supplemented with the interfering virus group(DIO+shPTGES3 group). The Morris water maze test was conducted to evaluate the cognitive behavior changes of the four groups of mice. The immunofluorescence staining was performed to detect the expression of PTGES3 and HSP90 in the medial prefrontal cortex and the activation of ionized calcium binding adapter molecule 1(IBA1)-labeled microglia.
Results:In the case-control study, the cognitive function of obese patients significantly decreased, and the expression of PTGES3 in peripheral blood significantly increased, while the level of PTGES3 was negatively correlated with cognitive function. In animal experiments, compared with ND group, DIO group had significantly prolonged time reaching the target platform, otherwise, the residence time in the target quadrant was shortened in the Morris water maze test. Simultaneously, there were significant increase in the expression of PTGES3 and HSP90, and the activation of IBA1 in the medial prefrontal cortex. Compared with DIO+Scramble group, mice in the DIO+shPTGES3 group spent less time reaching the target platform, and stayed longer in the target quadrant. The expression and co-localization levels of PTGES3 and HSP90 in medial prefrontal cortex significantly decreased. The activation level of microglia cells was also attenuated by PTGES3 interference.
Conclusion :Obesity-related cognitive dysfunction may be attributed to PTGES3/HSP90 in the medial prefrontal cortex by mediating neural inflammation.
- Full text:2026012609192842996内侧前额叶皮质PTGES3...肥胖相关认知障碍的机制研究_汪堇颜.pdf
