ArticleFrontiers in molecular neuroscience2012
Acetylcholinesterase loosens the brain's cholinergic anti-inflammatory response and promotes epileptogenesis.
Article in Frontiers in molecular neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 61 citations in OpenAlex.
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- A Near-Infrared Fluorescent Probe for Visualization of Acetylcholinesterase Flux in the Acute Epileptic Mice Brain.Chemical & biomedical imaging · 2025Article
- Unraveling the neuroprotective effect of perampanel and lacosamide combination in the corneal kindling model for epilepsy in mice.Animal models and experimental medicine · 2025Article
- Crisis in the gut: navigating gastrointestinal challenges in Gulf War Illness with bioengineering.Military Medical Research · 2024Review
- Current state of the epilepsy drug and device pipeline.Epilepsia · 2024Review
- Assessment of Biochemical and Neuroactivities of Cultural Filtrate fromLife (Basel, Switzerland) · 2023Article
- Neuroprotective Effects of Theobromine in permanent bilateral common carotid artery occlusion rat model of cerebral hypoperfusion.Metabolic brain disease · 2022Article
- Acrylamide Neurotoxicity as a Possible Factor Responsible for Inflammation in the Cholinergic Nervous System.International journal of molecular sciences · 2022Review
- Characterization of Immune-Related Genes and Immune Infiltration Features in Epilepsy by Multi-Transcriptome Data.Journal of inflammation research · 2022Article
- Cholinergic and Neuroimmune Signaling Interact to Impact Adult Hippocampal Neurogenesis and Alcohol Pathology Across Development.Frontiers in pharmacology · 2022Review
- Role of the Cholinergic Anti-Inflammatory Reflex in Central Nervous System Diseases.International journal of molecular sciences · 2021Review
- Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- 1,3,4, Oxadiazole Compound A3 Provides Robust Protection Against PTZ-Induced Neuroinflammation and Oxidative Stress by RegulatingJournal of inflammation research · 2021Article
- Acetylcholinesterase and human cancers.Advances in cancer research · 2021Review
- Carveol Attenuates Seizure Severity and Neuroinflammation in Pentylenetetrazole-Kindled Epileptic Rats by Regulating theOxidative medicine and cellular longevity · 2021Article
- Involvement of the Cholinergic Parameters and Glial Cells in Learning Delay Induced by Glutaric Acid: Protection by N-Acetylcysteine.Molecular neurobiology · 2019Article
- Evaluation of neurotoxicity and hepatotoxicity effects of acute and sub-acute oral administration of unripe ackee (Toxicology reports · 2019Article
- Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action.Journal of physiology and biochemistry · 2018Article
- Neuroprotective evidence of alpha-lipoic acid and desvenlafaxine on memory deficit in a neuroendocrine model of depression.Naunyn-Schmiedeberg's archives of pharmacology · 2018Article
- Glioprotective Effects of Lingonberry Extract Against Altered Cellular Viability, Acetylcholinesterase Activity, and Oxidative Stress in Lipopolysaccharide-Treated Astrocytes.Cellular and molecular neurobiology · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies show a key role of brain inflammation in epilepsy. However, the mechanisms controlling brain immune response are only partly understood. In the periphery, acetylcholine (ACh) release by the vagus nerve restrains inflammation by inhibiting the activation of leukocytes. Recent reports suggested a similar anti-inflammatory effect for ACh in the brain. Since brain cholinergic dysfunctions are documented in epileptic animals, we explored changes in brain cholinergic gene expression and associated immune response during pilocarpine-induced epileptogenesis. Levels of acetylcholinesterase (AChE) and inflammatory markers were measured using real-time RT-PCR, in-situ hybridization and immunostaining in wild type (WT) and transgenic mice over-expressing the "synaptic" splice variant AChE-S (TgS). One month following pilocarpine, mice were video-monitored for spontaneous seizures. To test directly the effect of ACh on the brain's innate immune response, cytokines expression levels were measured in acute brain slices treated with cholinergic agents. We report a robust up-regulation of AChE as early as 48 h following pilocarpine-induced status epilepticus (SE). AChE was expressed in hippocampal neurons, microglia, and endothelial cells but rarely in astrocytes. TgS mice overexpressing AChE showed constitutive increased microglial activation, elevated levels of pro-inflammatory cytokines 48 h after SE and accelerated epileptogenesis compared to their WT counterparts. Finally we show a direct, muscarine-receptor dependant, nicotine-receptor independent anti-inflammatory effect of ACh in brain slices maintained ex vivo. Our work demonstrates for the first time, that ACh directly suppresses brain innate immune response and that AChE up-regulation after SE is associated with enhanced immune response, facilitating the epileptogenic process. Our results highlight the cholinergic system as a potential new target for the prevention of seizures and epilepsy.
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