Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Mol Neurobiol
2016 Dec 01;5310:6635-6643. doi: 10.1007/s12035-015-9538-y.
Show Gene links
Show Anatomy links
The Role of Acetylcholine in the Inflammatory Response in Animals Surviving Sepsis Induced by Cecal Ligation and Puncture.
Jeremias IC
,
Victorino VJ
,
Barbeiro HV
,
Kubo SA
,
Prado CM
,
Lima TM
,
Soriano FG
.
???displayArticle.abstract???
The cholinergic anti-inflammatory pathway controls the inflammatory response and nonreflexive consciousness through bidirectional communication between the brain and immune system. Moreover, brain acetylcholinesterase activity may have a role in regulating the vagus nerve in this pathway. Thus, we analyzed the role of acetylcholine (ACh) in the inflammatory response 15 days after induction of sepsis by cecal ligation and puncture (CLP). Balb/c mice were pretreated with or without donepezil (5 mg/kg/day, orally) 7 days before CLP, and mice homozygous for vesicular ACh transporter (VAChT) knockdown (KD) were subjected to CLP. All animals were sacrificed 15 days after CLP, and the plasma, spleen, and hippocampus were collected. Characterization of splenic lymphocytes and cytokine levels in the plasma, spleen, and hippocampus was determined. Our results showed a splenomegaly in group CLP. The numbers of cytotoxic T cells, helper T cells, regulatory T cells, B cells, and Th17 cells differed between mice subjected to CLP and to sham operation in both untreated and donepezil-treated groups. In VAChT-KD mice, CLP resulted in decreased cytotoxic and helper T cells and increased in Th17 cells compared with the sham. Additionally, in VAChT-KD mice, the levels of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, were increased following CLP. Thus, we concluded that ACh affected the inflammatory response at 15 days after CLP since stimulation of cholinergic transmission increased the proliferation of lymphocytes, including regulatory T cells, in association with a lower inflammatory profile and VAChT-KD decreased the number of lymphocytes and increased inflammation.
Ayala,
Pathological aspects of apoptosis in severe sepsis and shock?
2003, Pubmed
Ayala,
Pathological aspects of apoptosis in severe sepsis and shock?
2003,
Pubmed
Balk,
The septic syndrome. Definition and clinical implications.
1989,
Pubmed
Barbeiro,
B-1 cells temper endotoxemic inflammatory responses.
2011,
Pubmed
Barbosa,
Expression of the vesicular acetylcholine transporter, proteins involved in exocytosis, and functional calcium signaling in varicosities and soma of a murine septal cell line.
1999,
Pubmed
Barbosa,
Trafficking of the vesicular acetylcholine transporter in SN56 cells: a dynamin-sensitive step and interaction with the AP-2 adaptor complex.
2002,
Pubmed
Borovikova,
Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin.
2000,
Pubmed
Francis,
The cholinergic hypothesis of Alzheimer's disease: a review of progress.
1999,
Pubmed
Gallowitsch-Puerta,
Neuro-immune interactions via the cholinergic anti-inflammatory pathway.
2007,
Pubmed
Giacobini,
Pharmacotherapy of Alzheimer disease: new drugs and novel strategies.
1993,
Pubmed
Gomez,
Immunological characterization of compensatory anti-inflammatory response syndrome in patients with severe sepsis: a longitudinal study*.
2014,
Pubmed
Gotoh,
Vagally mediated insulin secretion by stimulation of brain cholinergic neurons with neostigmine in bilateral adrenalectomized rats.
1989,
Pubmed
Hansen,
Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis.
2008,
Pubmed
Hoesel,
New insights into cellular mechanisms during sepsis.
2006,
Pubmed
Hofer,
Pharmacologic cholinesterase inhibition improves survival in experimental sepsis.
2008,
Pubmed
Hotchkiss,
Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy.
2013,
Pubmed
Hotchkiss,
The pathophysiology and treatment of sepsis.
2003,
Pubmed
Huston,
Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis.
2006,
Pubmed
Karima,
The molecular pathogenesis of endotoxic shock and organ failure.
1999,
Pubmed
Kunze,
Metabolic encephalopathies.
2002,
Pubmed
Lima,
Quantal release of acetylcholine in mice with reduced levels of the vesicular acetylcholine transporter.
2010,
Pubmed
Lorigados,
Pathomechanisms of myocardial dysfunction in sepsis.
2010,
Pubmed
Melo,
Endotoxin tolerance: selective alterations in gene expression and protection against lymphocyte death.
2010,
Pubmed
Olofsson,
Rethinking inflammation: neural circuits in the regulation of immunity.
2012,
Pubmed
Ono,
Removal of increased circulating CD4+CD25+Foxp3+ regulatory T cells in patients with septic shock using hemoperfusion with polymyxin B-immobilized fibers.
2013,
Pubmed
Osler,
Remarks ON THE FUNCTIONS OF AN OUT-PATIENT DEPARTMENT: Made at the Opening of the New Out - patient Department, Cardiff Infirmary, May 20th, 1908.
1908,
Pubmed
Pavlov,
Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis.
2007,
Pubmed
Pavlov,
Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway.
2009,
Pubmed
Pavlov,
Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia.
2006,
Pubmed
Pavlov,
The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation.
2003,
Pubmed
Pinheiro,
Pulmonary inflammation is regulated by the levels of the vesicular acetylcholine transporter.
2015,
Pubmed
,
Echinobase
Pozo,
Splenomegaly: investigation, diagnosis and management.
2009,
Pubmed
Prado,
Regulation of acetylcholine synthesis and storage.
2002,
Pubmed
Prado,
Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition.
2006,
Pubmed
Rosas-Ballina,
Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.
2011,
Pubmed
Rosas-Ballina,
Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia.
2008,
Pubmed
Santos,
Trafficking of green fluorescent protein tagged-vesicular acetylcholine transporter to varicosities in a cholinergic cell line.
2001,
Pubmed
Soriano,
Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice.
2002,
Pubmed
Tracey,
Physiology and immunology of the cholinergic antiinflammatory pathway.
2007,
Pubmed
Tracey,
The inflammatory reflex.
2003,
Pubmed
Valdés-Ferrer,
HMGB1 mediates splenomegaly and expansion of splenic CD11b+ Ly-6C(high) inflammatory monocytes in murine sepsis survivors.
2013,
Pubmed
Vandijck,
The value of sepsis definitions in daily ICU-practice.
2006,
Pubmed
van Westerloo,
The cholinergic anti-inflammatory pathway regulates the host response during septic peritonitis.
2005,
Pubmed
