Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

doi:10.1007/s11064-023-03994-w

. 2023 Dec;48(12):3512-3524.

doi: 10.1007/s11064-023-03994-w. Epub 2023 Jul 20.

Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

Dandan Lin¹, Yi Sun¹, Yuzhu Wang¹, Di Yang¹, Min Shui², Yiming Wang³, Ziyi Xue⁴, Xiao Huang¹, Yan Zhang^#⁵, Anshi Wu^#⁶, Changwei Wei^#⁷

Affiliations

¹ Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, China.
² Department of Anesthesiology, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, University of Electronic Science and Technology of China, Chengdu, China.
³ State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100871, China.
⁴ Department of Anesthesiology, Peking University First Hospital, Beijing, China.
⁵ State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100871, China. yanzhang@pku.edu.cn.
⁶ Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, China. wuanshi1965@163.com.
⁷ Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, China. changwei.wei@ccmu.edu.cn.

^# Contributed equally.

PMID: 37470907
DOI: 10.1007/s11064-023-03994-w

Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

Dandan Lin et al. Neurochem Res. 2023 Dec.

. 2023 Dec;48(12):3512-3524.

doi: 10.1007/s11064-023-03994-w. Epub 2023 Jul 20.

Authors

Dandan Lin¹, Yi Sun¹, Yuzhu Wang¹, Di Yang¹, Min Shui², Yiming Wang³, Ziyi Xue⁴, Xiao Huang¹, Yan Zhang^#⁵, Anshi Wu^#⁶, Changwei Wei^#⁷

Affiliations

¹ Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, China.
² Department of Anesthesiology, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, University of Electronic Science and Technology of China, Chengdu, China.
³ State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100871, China.
⁴ Department of Anesthesiology, Peking University First Hospital, Beijing, China.
⁵ State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100871, China. yanzhang@pku.edu.cn.
⁶ Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, China. wuanshi1965@163.com.
⁷ Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti Nanlu, Chao-Yang District, Beijing, 100020, China. changwei.wei@ccmu.edu.cn.

^# Contributed equally.

PMID: 37470907
DOI: 10.1007/s11064-023-03994-w

Abstract

Perioperative neurocognitive disorder (PND) is a common complication of surgery and anesthesia, especially among older patients. Microglial activation plays a crucial role in the occurrence and development of PND and transforming growth factor beta 1 (TGF-β1) can regulate microglial homeostasis. In the present study, abdominal surgery was performed on 12-14 months-old C57BL/6 mice to establish a PND model. The expression of TGF-β1, TGF-β receptor 1, TGF-β receptor 2, and phosphor-smad2/smad3 (psmad2/smad3) was assessed after anesthesia and surgery. Additionally, we examined changes in microglial activation, morphology, and polarization, as well as neuroinflammation and dendritic spine density in the hippocampus. Behavioral tests, including the Morris water maze and open field tests, were used to examine cognitive function, exploratory locomotion, and emotions. We observed decreased TGF-β1 expression after surgery and anesthesia. Intranasally administered exogenous TGF-β1 increased psmad2/smad3 colocalization with microglia positive for ionized calcium-binding adaptor molecule 1. TGF-β1 treatment attenuated microglial activation, reduced microglial phagocytosis, and reduced surgery- and anesthesia-induced changes in microglial morphology. Compared with the surgery group, TGF-β1 treatment decreased M1 microglial polarization and increased M2 microglial polarization. Additionally, surgery- and anesthesia-induced increase in interleukin 1 beta and tumor necrosis factor-alpha levels was ameliorated by TGF-β1 treatment at postoperative day 3. TGF-β1 also ameliorated cognitive function after surgery and anesthesia as well as rescue dendritic spine loss. In conclusion, surgery and anesthesia induced decrease in TGF-β1 levels in older mice, which may contribute to PND development; however, TGF-β1 ameliorated microglial activation and cognitive dysfunction in PND mice.

Keywords: Transforming growth factor beta 1; microglia; neuroinflammation; perioperative neurocognitive disorder; synapse.

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References

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[1] Jin Z, Hu J, Ma D (2020) Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth 125:492–504. https://doi.org/10.1016/j.bja.2020.06.063 - DOI - PubMed

[2] Jin Z, Hu J, Ma D (2020) Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth 125:492–504. https://doi.org/10.1016/j.bja.2020.06.063 - DOI - PubMed

[3] Needham MJ, Webb CE, Bryden DC (2017) Postoperative cognitive dysfunction and dementia: what we need to know and do. Br J Anaesth 119:i115–i125. https://doi.org/10.1093/bja/aex354 - DOI - PubMed

[4] Needham MJ, Webb CE, Bryden DC (2017) Postoperative cognitive dysfunction and dementia: what we need to know and do. Br J Anaesth 119:i115–i125. https://doi.org/10.1093/bja/aex354 - DOI - PubMed

[5] Feng X, Valdearcos M, Uchida Y, Lutrin D, Maze M, Koliwad SK (2017) Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice. JCI insight 2:e91229. https://doi.org/10.1172/jci.insight.91229 - DOI - PubMed - PMC

[6] Feng X, Valdearcos M, Uchida Y, Lutrin D, Maze M, Koliwad SK (2017) Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice. JCI insight 2:e91229. https://doi.org/10.1172/jci.insight.91229 - DOI - PubMed - PMC

[7] Subramaniyan S, Terrando N (2019) Neuroinflammation and perioperative neurocognitive disorders. Anesth Analg 128:781–788. https://doi.org/10.1213/ane.0000000000004053 - DOI - PubMed - PMC

[8] Subramaniyan S, Terrando N (2019) Neuroinflammation and perioperative neurocognitive disorders. Anesth Analg 128:781–788. https://doi.org/10.1213/ane.0000000000004053 - DOI - PubMed - PMC

[9] Deczkowska A, Keren-Shaul H, Weiner A, Colonna M, Schwartz M, Amit I (2018) Disease-associated microglia: a universal immune sensor of neurodegeneration. Cell 173:1073–1081. https://doi.org/10.1016/j.cell.2018.05.003 - DOI - PubMed

[10] Deczkowska A, Keren-Shaul H, Weiner A, Colonna M, Schwartz M, Amit I (2018) Disease-associated microglia: a universal immune sensor of neurodegeneration. Cell 173:1073–1081. https://doi.org/10.1016/j.cell.2018.05.003 - DOI - PubMed

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Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

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Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders

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