Abstract
Postoperative cognitive dysfunction (POCD) is characterized by cognitive impairments following anesthesia/surgery, but the role of obesity and the underlying mechanisms are not known. We investigated the impact of obesity on POCD. Eighty male C57BL/6 J mice were assigned randomly to two groups fed a normal chow diet (ND, n = 40) or a high-fat diet (HD, n = 40) for 20 weeks. Then, they were divided randomly into eight subgroups of 10: ND control (NDC), ND with surgery (NDS), HD control (HDC), HD with surgery (HDS); NDS + DMSO (NDS + DS), NDS + SRT1720 (NDS + SRT), HDS + DMSO (HDS + DS), and HDS + SRT1720 (HDS + SRT). Body weight, blood glucose level, and serum lipid levels were measured. Staining methods on liver tissues were used to determine hepatic steatosis. A POCD model was established by sleeve gastrectomy (SG) under isoflurane anesthesia. Cognitive function was assessed using the Morris water maze test (MWMT). Expression of sirtuin1 (SIRT1), phosphorylated cAMP-responsive element binding protein (p-CREB), CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. High-fat diet-fed mice for 20 weeks could establish an obesity model with hyperlipidemia and hepatic steatosis. Cognitive impairment was significantly worse in the HDC and HDS groups than that in the NDC and NDS groups, respectively. Hippocampal expression of SIRT1, p-CREB, and BDNF in the HDS group was significantly lower than that of the HDC group. SRT1720 (SIRT1 activator) pretreatment could attenuate cognitive impairment by upregulating SIRT1 expression. These data suggest that obesity exacerbated postoperative hippocampal-dependent cognitive impairment via a SIRT1 pathway, and SRT1720 pretreatment could alleviate it.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Amidfar M, de Oliveira J, Kucharska E, Budni J, Kim YK (2020) The role of CREB and BDNF in neurobiology and treatment of Alzheimer’s disease. Life Sci 257:118020. https://doi.org/10.1016/j.lfs.2020.118020
Baiges-Gaya G, Fernandez-Arroyo S, Luciano-Mateo F et al (2020) Hepatic metabolic adaptation and adipose tissue expansion are altered in mice with steatohepatitis induced by high-fat high sucrose diet. J Nutr Biochem 89:108559. https://doi.org/10.1016/j.jnutbio.2020.108559
Brigadski T, Lessmann V (2020) The physiology of regulated BDNF release. Cell Tissue Res 382:15–45. https://doi.org/10.1007/s00441-020-03253-2
Bruinsma BG, Uygun K, Yarmush ML, Saeidi N (2015) Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice. Nat Protoc 10:495–507. https://doi.org/10.1038/nprot.2015.027
Cao Y, Yan Z, Zhou T, Wang G (2017) SIRT1 regulates cognitive performance and ability of learning and memory in diabetic and nondiabetic models. J Diabetes Res 2017:7121827. https://doi.org/10.1155/2017/7121827
Cheng XQ, Mei B, Zuo YM et al (2019) A multicentre randomised controlled trial of the effect of intra-operative dexmedetomidine on cognitive decline after surgery. Anaesthesia 74:741–750. https://doi.org/10.1111/anae.14606
Evered L, Silbert B, Knopman DS et al (2018) Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth 121:1005–1012. https://doi.org/10.1016/j.bja.2017.11.087
Feng C, Gu J, Zhou F et al (2016) The effect of lead exposure on expression of SIRT1 in the rat hippocampus. Environ Toxicol Pharmacol 44:84–92. https://doi.org/10.1016/j.etap.2016.04.008
Herskovits AZ, Guarente L (2014) SIRT1 in neurodevelopment and brain senescence. Neuron 81:471–483. https://doi.org/10.1016/j.neuron.2014.01.028
Jiao F, Gong Z (2020) The beneficial roles of SIRT1 in neuroinflammation-related diseases. Oxid Med Cell Longev 2020:6782872. https://doi.org/10.1155/2020/6782872
Kim JY, Barua S, Jeong YJ, Lee JE (2020) Adiponectin: the potential regulator and therapeutic target of obesity and Alzheimer’s disease. Int J Mol Sci. https://doi.org/10.3390/ijms21176419
Kotagale N, Rahmatkar S, Chauragade S, Dixit M, Umekar M, Chopde C, Taksande B (2020) Involvement of hippocampal agmatine in beta1-42 amyloid induced memory impairment, neuroinflammation and BDNF signaling disruption in mice. Neurotoxicology 80:1–11. https://doi.org/10.1016/j.neuro.2020.06.002
Lima Giacobbo B, Doorduin J, Klein HC, Dierckx R, Bromberg E, de Vries EFJ (2019) Brain-derived neurotrophic factor in brain disorders: focus on neuroinflammation. Mol Neurobiol 56:3295–3312. https://doi.org/10.1007/s12035-018-1283-6
Ma Y, Fan Y, Zhou D, Chen J, Ge S (2021) Laparoscopic sleeve gastrectomy under general anesthesia in severely obese patients: a single-centered retrospective study. PeerJ 9:e10802. https://doi.org/10.7717/peerj.10802
Mishra P, Mittal AK, Kalonia H, Madan S, Ghosh S, Sinha JK, Rajput SK (2020) SIRT1 promotes neuronal fortification in neurodegenerative diseases through attenuation of pathological hallmarks and enhancement of cellular lifespan. Curr Neuropharmacol. https://doi.org/10.2174/1570159X18666200729111744
Ng TKS, Ho CSH, Tam WWS, Kua EH, Ho RC (2019) Decreased serum brain-derived neurotrophic factor (BDNF) levels in patients with Alzheimer’s disease (AD): a systematic review and meta-analysis. Int J Mol Sci. https://doi.org/10.3390/ijms20020257
Niu B, He K, Li P et al (2018) SIRT1 upregulation protects against liver injury induced by a HFD through inhibiting CD36 and the NFkappaB pathway in mouse kupffer cells. Mol Med Rep 18:1609–1615. https://doi.org/10.3892/mmr.2018.9088
O’Brien PD, Hinder LM, Callaghan BC, Feldman EL (2017) Neurological consequences of obesity. Lancet Neurol 16:465–477. https://doi.org/10.1016/S1474-4422(17)30084-4
Schipke CG, Menne F, Rubow S, Sigle JP, Peters O, Grimmer T (2020) Value of a panel of 6 serum biomarkers to differentiate between healthy controls and mild cognitive impairment due to Alzheimer disease. Alzheimer Dis Assoc Disord 34:318–324. https://doi.org/10.1097/WAD.0000000000000397
Shi J, Zou X, Jiang K, Wang F (2020) SIRT1 mediates improvement of cardiac surgery-induced postoperative cognitive dysfunction via the TLR4/NF-kappaB pathway. World J Biol Psychiatry 21:757–765. https://doi.org/10.1080/15622975.2019.1656820
Shi J, Zou X, Jiang K, Wang F (2019) SIRT1 mediates improvement of cardiac surgery-induced postoperative cognitive dysfunction via the TLR4/NF-kappaB pathway. World J Biol Psychiatry 21:1–9. https://doi.org/10.1080/15622975.2019.1656820
Yu Y, Zhao Y, Teng F et al (2018) berberine improves cognitive deficiency and muscular dysfunction via activation of the AMPK/SIRT1/PGC-1a pathway in skeletal muscle from naturally aging rats. J Nutr Health Aging 22:710–717. https://doi.org/10.1007/s12603-018-1015-7
Acknowledgements
We thank the Department of Biostatistics, Zhongshan Hospital, Fudan University for their assistance.
Funding
This study was supported by the Shanghai Association for Science and Technology (20ZR1410700).
Author information
Authors and Affiliations
Contributions
YM designed the study, conducted most of the experiments, analyzed the data and results, and wrote the manuscript. YJ participated in the data and results analysis. L.X. participated in the animal-behavior test. ZL participated in animal experiments. SG designed and improved the study and revised the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Ethics approval
This study was approved by the Animal Ethical Committee of Zhongshan Hospital, Fudan University. All experimental procedures were performed in accordance with relevant guidelines and regulations.
Additional information
Communicated by Sreedharan Sajikumar.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Ma, Y., Ji, Y., Xu, L. et al. Obesity aggravated hippocampal-dependent cognitive impairment after sleeve gastrectomy in C57/BL6J mice via SIRT1/CREB/BDNF pathway. Exp Brain Res 240, 2897–2906 (2022). https://doi.org/10.1007/s00221-022-06465-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00221-022-06465-w