Metabolic reprogramming mediates hippocampal microglial M1 polarization in response to surgical trauma causing perioperative neurocognitive disorders

Luo, Gang; Wang, Xiaofeng; Cui, Yongchen; Cao, Yue; Zhao, Zhe; Zhang, Junfeng

doi:10.1186/s12974-021-02318-5

Cited by 50 publications

(23 citation statements)

References 53 publications

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“…Surgery and anesthetics spark systemic inflammatory cytokines and damage the blood-brain barrier, thereby sending harmful chemicals and cells into the brain and activating microglia, which further contribute to neuroinflammation (Mahanna-Gabrielli et al, 2019;Yang et al, 2020). The specificity of reactive microgliosis and IL-1β involvement in PNDs has been revealed by previous studies (Luo et al, 2021). Circulating IL-1β and hippocampal IL-1β levels are consistently upregulated after surgery and anesthesia, in preclinical models, and in surgical patients (Skvarc et al, 2018).…”

Section: Anti-inflammatory Response Induced By α7nachr Stimulation In...mentioning

confidence: 90%

α7 Nicotinic Acetylcholine Receptor May Be a Pharmacological Target for Perioperative Neurocognitive Disorders

Wei

Lyu

et al. 2022

Front. Pharmacol.

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Background: The α7 nicotinic acetylcholine receptor (α7nAChR) is a promising therapeutic target in neurodegenerative diseases. This study examined the effects of surgery and anesthesia on α7nAChR expression in the central nervous system and determined the mechanisms by which α7nAChR mediates neuroprotection in perioperative neurocognitive disorders (PNDs) in aged mice.Methods: Eighteen-month-old male C57BL/6J mice underwent aseptic laparotomy under isoflurane anesthesia, maintaining spontaneous ventilation to establish the PNDs model. Agonists and antagonists of the α7nAChR and tropomyosin receptor kinase B (TrkB) receptors were administered before anesthesia. The α7nAChR expression, peripheral as well as hippocampal interleukin-1β (IL-1β), and the brain-derived neurotrophic factor (BDNF) levels were assessed. Separate cohorts of aged mice were tested for cognitive decline using the Morris water maze (MWM).Results: Surgery and anesthesia significantly suppressed α7nAChR expression in the hippocampus and cortex. Surgery-induced IL-1β upregulation in the serum as well as hippocampus and hippocampal microglial activation were reversed by the α7nAChR agonist. A significant reduction in the hippocampal BDNF levels were also observed. The α7nAChR stimulation reversed, and α7nAChR suppression promoted BDNF reduction in the hippocampus. Blocking the BDNF/TrkB signaling pathway abolished α7nAChR-induced neuroprotection in PNDs, as evidenced by poor cognitive performance in the MWM test.Conclusions: These data reveal that α7nAChR plays a key role in PNDs. The mechanisms of the anti-inflammatory pathway and BDNF/TrkB signaling pathways are involved in α7nAChR-meidiated neuroprotection in PNDs.

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Section: Anti-inflammatory Response Induced By α7nachr Stimulation In...mentioning

confidence: 90%

α7 Nicotinic Acetylcholine Receptor May Be a Pharmacological Target for Perioperative Neurocognitive Disorders

Wei

Lyu

et al. 2022

Front. Pharmacol.

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“…Neuroinflammation still runs through the study of these diseases. Finally, it is worth mentioning that the minor groups, mitochondria, and glycolysis groups, suggest that attention has been paid to the transformation of energy metabolism in the activation process of microglia, which is called metabolic reprogramming ( Baik et al, 2019 ; Bernier et al, 2020 ; Gu et al, 2021 ; Luo et al, 2021 ). It might also be a reference point for microglia with abnormal phenotypic change and function.…”

Section: Discussionmentioning

confidence: 99%

Knowledge domains and emerging trends of microglia research from 2002 to 2021: A bibliometric analysis and visualization study

Liu

Yang

et al. 2023

Front. Aging Neurosci.

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BackgroundMicroglia have been identified for a century. In this period, their ontogeny and functions have come to light thanks to the tireless efforts of scientists. However, numerous documents are being produced, making it challenging for scholars, especially those new to the field, to understand them thoroughly. Therefore, having a reliable method for quickly grasping a field is crucial.MethodsWe searched and downloaded articles from the Web of Science Core Collection with “microglia” or “microglial” in the title from 2002 to 2021. Eventually, 12,813 articles were located and, using CiteSpace and VOSviewer, the fundamental data, knowledge domains, hot spots, and emerging trends, as well as the influential literature in the field of microglia research, were analyzed.ResultsFollowing 2011, microglia publications grew significantly. The two prominent journals are Glia and J Neuroinflamm. The United States and Germany dominated the microglia study. The primary research institutions are Harvard Univ and Univ Freiburg, and the leading authors are Prinz Marco and Kettenmann Helmut. The knowledge domains of microglia include eight directions, namely neuroinflammation, lipopolysaccharide, aging, neuropathic pain, macrophages, Alzheimer’s disease, retina, and apoptosis. Microglial phenotype is the focus of research; while RNA-seq, exosome, and glycolysis are emerging topics, a microglial-specific marker is still a hard stone. We also identified 19 influential articles that contributed to the study of microglial origin (Mildner A 2007; Ginhoux F 2010), identity (Butovsky O 2014), homeostasis (Cardona AE 2006; Elmore MRP 2014); microglial function such as surveillance (Nimmerjahn A 2005), movement (Davalos D 2005; Haynes SE 2006), phagocytosis (Simard AR 2006), and synapse pruning (Wake H 2009; Paolicelli RC 2011; Schafer DP 2012; Parkhurst CN 2013); and microglial state/phenotype associated with disease (Keren-Shaul H 2017), as well as 5 review articles represented by Kettenmann H 2011.ConclusionUsing bibliometrics, we have investigated the fundamental data, knowledge structure, and dynamic evolution of microglia research over the previous 20 years. We hope this study can provide some inspiration and a reference for researchers studying microglia in neuroscience.

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“…As highly dynamic cells, microglia carry out a non-stop patrol of the CNS, rapidly activate and exhibit either M1 or M2 phenotype to maintain brain homeostasis (Tang and Le, 2016). Accumulating evidence supports that microglia exhibit different metabolic profiles in the face of alterations in the microenvironment, that to support morphological changes and functional remodeling in the process of cell polarization (Orihuela et al, 2016;Luo et al, 2021). Insulin is necessary for metabolism regulation and bioenergy production by regulating cellular glucose transport (Summers et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemia-induced microglial mitochondrial dynamic and metabolic alterations lead to neuroinflammation in vivo and in vitro

Yang

Gao

et al. 2022

Front. Neurosci.

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Numerous studies have demonstrated that type 2 diabetes (T2D) is closely linked to the occurrence of Alzheimer’s disease (AD). Nevertheless, the underlying mechanisms for this association are still unknown. Insulin resistance (IR) hallmarked by hyperinsulinemia, as the earliest and longest-lasting pathological change in T2D, might play an important role in AD. Since hyperinsulinemia has an independent contribution to related disease progressions by promoting inflammation in the peripheral system, we hypothesized that hyperinsulinemia might have an effect on microglia which plays a crucial role in neuroinflammation of AD. In the present study, we fed 4-week-old male C57BL/6 mice with a high-fat diet (HFD) for 12 weeks to establish IR model, and the mice treated with standard diet (SD) were used as control. HFD led to obesity in mice with obvious glucose and lipid metabolism disorder, the higher insulin levels in both plasma and cerebrospinal fluid, and aberrant insulin signaling pathway in the whole brain. Meanwhile, IR mice appeared impairments of spatial learning and memory accompanied by neuroinflammation which was characterized by activated microglia and upregulated expression of pro-inflammatory factors in different brain regions. To clarify whether insulin contributes to microglial activation, we treated primary cultured microglia and BV2 cell lines with insulin in vitro to mimic hyperinsulinemia. We found that hyperinsulinemia not only increased microglial proliferation and promoted M1 polarization by enhancing the production of pro-inflammatory factors, but also impaired membrane translocation of glucose transporter 4 (GLUT4) serving as the insulin-responding glucose transporter in the processes of glucose up-taking, reduced ATP production and increased mitochondrial fission. Our study provides new perspectives and evidence for the mechanism underlying the association between T2D and AD.

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Metabolic reprogramming mediates hippocampal microglial M1 polarization in response to surgical trauma causing perioperative neurocognitive disorders

Cited by 50 publications

References 53 publications

α7 Nicotinic Acetylcholine Receptor May Be a Pharmacological Target for Perioperative Neurocognitive Disorders

α7 Nicotinic Acetylcholine Receptor May Be a Pharmacological Target for Perioperative Neurocognitive Disorders

Knowledge domains and emerging trends of microglia research from 2002 to 2021: A bibliometric analysis and visualization study

Hyperinsulinemia-induced microglial mitochondrial dynamic and metabolic alterations lead to neuroinflammation in vivo and in vitro

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