Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stress
The purposes of this study were to explore the impact of obesity on postoperative cognitive dysfunction (POCD) and to investigate the underlying mechanism by which obesity exacerbates POCD. In this study, fifteen-month-old male C57BL/6 J mice were fed a High-fat diet for three months to establish ob...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556523002413 |
| _version_ | 1797616031845318656 |
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| author | Li Xu Yuanyuan Ma Yelong Ji Yimei Ma Ying Wang Xining Zhao Shengjin Ge |
| author_facet | Li Xu Yuanyuan Ma Yelong Ji Yimei Ma Ying Wang Xining Zhao Shengjin Ge |
| author_sort | Li Xu |
| collection | DOAJ |
| description | The purposes of this study were to explore the impact of obesity on postoperative cognitive dysfunction (POCD) and to investigate the underlying mechanism by which obesity exacerbates POCD. In this study, fifteen-month-old male C57BL/6 J mice were fed a High-fat diet for three months to establish obesity models. Internal fixation of tibial fractures under isoflurane inhalation was performed to construct a POCD animal model. Three days after surgery, mice were subjected to the Morris water maze (MWM) experiment to evaluate their learning and memory abilities. The findings from the MWM experiment revealed that in comparison to the Ad Libitum Surgical group (ALS), mice in the High-fat Surgical group (HFS) exhibited prolonged escape latencies and reduced platform crossings. These outcomes suggest the potential exacerbating role of obesity in cognitive impairment within the POCD mouse models. Immunofluorescence (IF) findings demonstrate that obesity intensifies anesthesia and surgery-induced oxidative stress levels within the hippocampus. Compared to the Ad Libitum Control group (ALC), an elevation in PARP1 expression and a reduction in the NAD+/NADH ratio and SIRT1 expression were observed in the hippocampus of mice from the ALS. Moreover, when contrasting the HFS group with the ALS group, increased PARP1 expression along with decreased NAD+/NADH ratio and SIRT1 expression were evident. In vitro studies found that compared with the Control group (CON), oil red staining and BODIPY probe staining showed significant lipid droplet aggregation in the palmitic acid (PA) group. IF results demonstrated that HT22 cells in the PA group experienced oxidative stress and activation of the PARP1/NAD+/SIRT1 axis in contrast to the CON group. Moreover, manipulation of PARP1 expression in HT22 cells through PARP1 lentivirus-based silencing or overexpression revealed a converse relationship between PARP1 expression levels and the NAD+/NADH ratio as well as SIRT1 expression levels. This study concludes that obesity may exacerbate POCD by triggering activation of the oxidative stress-induced PARP1/NAD+/SIRT1 axis. |
| first_indexed | 2024-03-11T07:35:24Z |
| format | Article |
| id | doaj.art-ea9e5d3c356449f4a3e229bbf181e0bd |
| institution | Directory Open Access Journal |
| issn | 1873-6815 |
| language | English |
| last_indexed | 2024-03-11T07:35:24Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj.art-ea9e5d3c356449f4a3e229bbf181e0bd2023-11-17T05:25:10ZengElsevierExperimental Gerontology1873-68152023-11-01183112320Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stressLi Xu0Yuanyuan Ma1Yelong Ji2Yimei Ma3Ying Wang4Xining Zhao5Shengjin Ge6Department of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaDepartment of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaDepartment of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaDepartment of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaDepartment of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaDepartment of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaCorresponding author.; Department of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaThe purposes of this study were to explore the impact of obesity on postoperative cognitive dysfunction (POCD) and to investigate the underlying mechanism by which obesity exacerbates POCD. In this study, fifteen-month-old male C57BL/6 J mice were fed a High-fat diet for three months to establish obesity models. Internal fixation of tibial fractures under isoflurane inhalation was performed to construct a POCD animal model. Three days after surgery, mice were subjected to the Morris water maze (MWM) experiment to evaluate their learning and memory abilities. The findings from the MWM experiment revealed that in comparison to the Ad Libitum Surgical group (ALS), mice in the High-fat Surgical group (HFS) exhibited prolonged escape latencies and reduced platform crossings. These outcomes suggest the potential exacerbating role of obesity in cognitive impairment within the POCD mouse models. Immunofluorescence (IF) findings demonstrate that obesity intensifies anesthesia and surgery-induced oxidative stress levels within the hippocampus. Compared to the Ad Libitum Control group (ALC), an elevation in PARP1 expression and a reduction in the NAD+/NADH ratio and SIRT1 expression were observed in the hippocampus of mice from the ALS. Moreover, when contrasting the HFS group with the ALS group, increased PARP1 expression along with decreased NAD+/NADH ratio and SIRT1 expression were evident. In vitro studies found that compared with the Control group (CON), oil red staining and BODIPY probe staining showed significant lipid droplet aggregation in the palmitic acid (PA) group. IF results demonstrated that HT22 cells in the PA group experienced oxidative stress and activation of the PARP1/NAD+/SIRT1 axis in contrast to the CON group. Moreover, manipulation of PARP1 expression in HT22 cells through PARP1 lentivirus-based silencing or overexpression revealed a converse relationship between PARP1 expression levels and the NAD+/NADH ratio as well as SIRT1 expression levels. This study concludes that obesity may exacerbate POCD by triggering activation of the oxidative stress-induced PARP1/NAD+/SIRT1 axis.http://www.sciencedirect.com/science/article/pii/S0531556523002413ObesityPostoperative cognitive dysfunctionOxidative stressPARP1NAD+SIRT1 |
| spellingShingle | Li Xu Yuanyuan Ma Yelong Ji Yimei Ma Ying Wang Xining Zhao Shengjin Ge Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stress Experimental Gerontology Obesity Postoperative cognitive dysfunction Oxidative stress PARP1 NAD+ SIRT1 |
| title | Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stress |
| title_full | Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stress |
| title_fullStr | Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stress |
| title_full_unstemmed | Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stress |
| title_short | Obesity exacerbates postoperative cognitive dysfunction by activating the PARP1/NAD+/SIRT1 axis through oxidative stress |
| title_sort | obesity exacerbates postoperative cognitive dysfunction by activating the parp1 nad sirt1 axis through oxidative stress |
| topic | Obesity Postoperative cognitive dysfunction Oxidative stress PARP1 NAD+ SIRT1 |
| url | http://www.sciencedirect.com/science/article/pii/S0531556523002413 |
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