Stimulation of toll-like receptor 4 downregulates the expression of α7 nicotinic acetylcholine receptors via histone deacetylase in rodent microglia

Nakamura, Yoki; Kimura, Sayuri; Takada, Naoki; Takemura, Masashi; Iwamoto, Momoka; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro; Morioka, Norimitsu

doi:10.1016/j.neuint.2020.104751

Cited by 14 publications

(7 citation statements)

References 80 publications

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“…Thus, α 7nAChR expression could be damaged by either dietary or inflammatory factors that could modulate the presence of the receptor in the membrane through different pathways. The methylation of CpG sites in the promoter region, the activation of histone deacetylase, and ubiquitination are possible mechanisms that could reduce the presence of the cholinergic receptor in the membrane [ 21 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response

Martins

Contieri

Amaral

et al. 2021

Mediators of Inflammation

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The study is aimed at investigating if PUFA supplementation could prevent the effects of a short-term HFD on α7nAChR expression and on the severity of sepsis. Swiss mice were used for the in vivo experiments. For the in vitro experiments, we used a microglia cell line (BV-2) and a hepatoma cell line (Hepa-1c1c7) derived from mice. The animals were either fed standard chow, fed a short-term HFD (60%), or given supplementation with omega-3 fatty acid (2 g/kg or 4 g/kg bw) for 17 days, followed by a short-term HFD. Endotoxemia was induced with an intraperitoneal (i.p.) lipopolysaccharide injection (LPS, 5 or 12 mg/kg), and sepsis was induced by subjecting the animals to cecal ligation and puncture (CLP). BV-2 and Hepa-1c1c7 cells were treated with LPS (100 and 500 ng/mL, respectively) for 3 hours. RT-PCR or Western blotting was used to evaluate α7nAChR expression, inflammatory markers, DNMT1, and overall ubiquitination. LPS and HFD reduced the expression of α7nAChR and increased the expression of inflammatory markers. Omega-3 partially prevented the damage caused by the HFD to the expression of α7nAChR in the bone marrow and hypothalamus, decreased the inflammatory markers, and reduced susceptibility to sepsis-induced death. Exposing the BV-2 cells to LPS increased the protein content of DNMT1 and the overall ubiquitination and reduced the expression of α7nAChR. The inflammation induced by LPS in the BV-2 cell decreased α7nAChR expression and concomitantly increased DNMT1 expression and the ubiquitinated protein levels, indicating the participation of pre- and posttranscriptional mechanisms.

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Section: Introductionmentioning

confidence: 99%

Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response

Martins

Contieri

Amaral

et al. 2021

Mediators of Inflammation

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“…In turn, nicotinic ACh receptor activation would mediate the TLR2 proinflammatory pathways involved in wound repair [ 50 ]. Other studies have described that the activation of TLR4 would control the expression of α7 nACh receptors in rodent microglia [ 51 ]. Although our results show that the absence of TLR4 alters the gut motility through changes in the expression or function of ACh muscarinic and nicotinic receptors, other non-cholinergic pathways have been reported to be involved [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors

Layunta

Forcén

Grasa

2022

Cells

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Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by intestinal dysmotility. Changes in intestinal microbiota (dysbiosis) can lead to alterations in neuro-muscular functions in the gut. Toll-like receptors (TLRs) 2 and 4 recognize intestinal bacteria and are involved in the motor response induced by gastrointestinal (GI) neurotransmitters. Acetylcholine (ACh) is a well-known neurotransmitter involved in the regulation of GI motility. This study aimed to evaluate the role of TLR2 and TLR4 in the intestinal motor-response induced by ACh in the mouse ileum, as well as the expression and function of the muscarinic and nicotinic ACh receptors. Muscle contractility studies showed that the contractions induced by ACh were significantly lower in TLR2−/− and TLR4−/− with respect to WT mice. In WT mice, the contractions induced by ACh were reduced in the presence of AF-DX AF-DX 116 (a muscarinic ACh receptor (mAChR) M2 antagonist), 4-DAMP (a mAChR M3 antagonist), mecamylamine (a nicotinic AChR receptor (nAChR) α3β4 antagonist) and α-bungarotoxin (a nAChR α7 antagonist). In TLR2−/− mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4−/− mice, the contractions induced by ACh were reduced by α-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and α3 receptors were diminished in the ileum from TLR2−/− and TLR4−/− with respect to WT mice. However, the levels of mRNA and protein of β4 were diminished only in TLR4−/− but not in TLR2−/− mice. In conclusion, our results show that TLR2 and TLR4 modulates the motor responses to ACh in the mouse ileum. TLR2 acts on muscarinic M2 and M3 and nicotinic α3β4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic α3β4 and α7 ACh receptors.

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“…One of its important functions is neuroprotection via secretion of anti inflammatory cytokines and neu rotrophic factors, primarily, brain derived neurotrophic factor (BDNF), thus facilitating neuron survival in the penumbra [34]. Expression of the α7 subunit containing nicotine acetylcholine receptor, crucial for the regulation of the neuroprotective function of microglia, decreased in response to neuroinflammation [35]. Protective phago cytic capacity of the microglia is normally low, but it increases under inflammatory conditions.…”

Section: Rapid Responses Of the Hippocampus To The Ischemic Damagementioning

confidence: 99%

Changes in Gene Expression and Neuroinflammation in the Hippocampus after Focal Brain Ischemia: Involvement in the Long-Term Cognitive and Mental Disorders

Шишкина

Калинина

Gulyaeva

et al. 2021

Biochemistry Moscow

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Ischemic brain injuries are accompanied by the long-term changes in gene expression in the hippocampus, the limbic system structure, involved in the regulation of key aspects of the higher nervous activity, such as cognitive functions and emotions. The altered expression of genes and proteins encoded by them may be related to the development of post-ischemic psycho-emotional and cognitive disturbances. Activation of neuroinflammation following stroke in the hippocampus has been suggested to play an essential role in induction of long-lasting consequences. Identification of changes in the gene expression patterns after ischemia and investigation of the dynamics of these changes in the hippocampus are the necessary first steps toward understanding molecular pathways responsible for the development of post-stroke cognitive impairments and mental pathologies.

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Stimulation of toll-like receptor 4 downregulates the expression of α7 nicotinic acetylcholine receptors via histone deacetylase in rodent microglia

Cited by 14 publications

References 80 publications

Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response

Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response

TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors

Changes in Gene Expression and Neuroinflammation in the Hippocampus after Focal Brain Ischemia: Involvement in the Long-Term Cognitive and Mental Disorders

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