PMID- 26637327
OWN - NLM
STAT- MEDLINE
DCOM- 20171229
LR  - 20181113
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 53
IP  - 10
DP  - 2016 Dec
TI  - The Role of Acetylcholine in the Inflammatory Response in Animals Surviving 
      Sepsis Induced by Cecal Ligation and Puncture.
PG  - 6635-6643
AB  - 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-1beta, IL-6, and TNF-alpha, 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.
FAU - Jeremias, I C
AU  - Jeremias IC
AUID- ORCID: 0000-0002-7096-8004
AD  - Laboratorio de Investigacao Medica - LIM 51, Faculdade de Medicina, Universidade 
      de Sao Paulo (FMUSP), Sao Paulo, Brazil. belacasagrandej@hotmail.com.
FAU - Victorino, V J
AU  - Victorino VJ
AD  - Laboratorio de Investigacao Medica - LIM 51, Faculdade de Medicina, Universidade 
      de Sao Paulo (FMUSP), Sao Paulo, Brazil.
FAU - Barbeiro, H V
AU  - Barbeiro HV
AD  - Laboratorio de Investigacao Medica - LIM 51, Faculdade de Medicina, Universidade 
      de Sao Paulo (FMUSP), Sao Paulo, Brazil.
FAU - Kubo, S A
AU  - Kubo SA
AD  - Laboratorio de Investigacao Medica - LIM 51, Faculdade de Medicina, Universidade 
      de Sao Paulo (FMUSP), Sao Paulo, Brazil.
FAU - Prado, C M
AU  - Prado CM
AD  - Departmento de Ciencias Biologicas, Universidade Federal de Sao Paulo, Diadema, 
      Brazil.
FAU - Lima, T M
AU  - Lima TM
AD  - Laboratorio de Investigacao Medica - LIM 51, Faculdade de Medicina, Universidade 
      de Sao Paulo (FMUSP), Sao Paulo, Brazil.
FAU - Soriano, F G
AU  - Soriano FG
AD  - Laboratorio de Investigacao Medica - LIM 51, Faculdade de Medicina, Universidade 
      de Sao Paulo (FMUSP), Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151205
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Cytokines)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/*pharmacology
MH  - Animals
MH  - Cecum/*pathology
MH  - Cytokines/blood/metabolism
MH  - Hippocampus/metabolism
MH  - Inflammation/*complications/*pathology
MH  - Ligation
MH  - Lymphocytes/pathology
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Organ Size
MH  - *Punctures
MH  - Sepsis/*complications/*pathology
MH  - Spleen/pathology
MH  - Survival Analysis
OTO - NOTNLM
OT  - Ach
OT  - Cytokines
OT  - Donepezil
OT  - Lymphocytes
OT  - Sepsis
OT  - VAChT
EDAT- 2015/12/08 06:00
MHDA- 2017/12/30 06:00
CRDT- 2015/12/06 06:00
PHST- 2015/06/05 00:00 [received]
PHST- 2015/11/09 00:00 [accepted]
PHST- 2015/12/08 06:00 [pubmed]
PHST- 2017/12/30 06:00 [medline]
PHST- 2015/12/06 06:00 [entrez]
AID - 10.1007/s12035-015-9538-y [pii]
AID - 10.1007/s12035-015-9538-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2016 Dec;53(10):6635-6643. doi: 10.1007/s12035-015-9538-y. Epub 
      2015 Dec 5.