PMID- 35413868
OWN - NLM
STAT- MEDLINE
DCOM- 20220414
LR  - 20220718
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 19
IP  - 1
DP  - 2022 Apr 12
TI  - Microglial cell response in alpha7 nicotinic acetylcholine receptor-deficient mice 
      after systemic infection with Escherichia coli.
PG  - 94
LID - 10.1186/s12974-022-02452-8 [doi]
LID - 94
AB  - BACKGROUND: Development of neurodegeneration in older people has been associated 
      with microglial cell activation triggered by systemic infection. We hypothesize 
      that alpha7 nicotinic acetylcholine receptor (alpha7nAChR) plays an important role in 
      regulation of this process. METHODS: 8- to 10-week-old male wild-type (WT) and 
      alpha7nAChR knock-out (alpha7nAChR(-/-)) mice were intraperitoneally inoculated with live 
      Escherichia (E.) coli or saline. After inoculation, all mice were treated with 
      ceftriaxone (an antimicrobial drug) at 12 and 24 h and killed at 2 or 3 days. The 
      microglial response was characterized by immunohistochemical staining with an 
      ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. 
      To quantify inflammatory response, mRNA expression of pro- and anti-inflammatory 
      mediators was measured in brain and spleen. RESULTS: We observed no differences 
      in Iba-1 positive cell number or morphology and flow cytometry (CD11b, CD45 and 
      CD14) of microglial cells between WT and alpha7nAChR(-/-) mice after systemic 
      infection. Infected alpha7nAChR(-/-) mice showed significantly higher mRNA expression 
      in brain for tumor necrosis factor alpha (TNF-alpha) at day 2 and 3, interleukin 6 
      (IL-6) at day 2 and monocyte chemotactic protein 1 (MCP-1) and suppressor of 
      cytokine signaling 1 (SOCS1) at day 3, there was significantly lower mRNA 
      expression in brain for mitogen-activated protein kinase 1 (MAPK1) at day 2 and 
      3, high-mobility group 1 (HMGB-1) and CD11b at day 2, and deubiquitinase protein 
      A20 (A20) at day 3 compared to infected WT mice. INTERPRETATION: Loss of function 
      of alpha7nAChR during systemic infection led to an increased expression of TNF-alpha and 
      IL-6 in brain after systemic infection with E. coli, but not to distinct 
      differences in microglial cell number or morphological activation of microglia.
CI  - (c) 2022. The Author(s).
FAU - Hoogland, Inge C M
AU  - Hoogland ICM
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - Yik, Jutka
AU  - Yik J
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - Westhoff, Dunja
AU  - Westhoff D
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - Engelen-Lee, Joo-Yeon
AU  - Engelen-Lee JY
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - Valls Seron, Merche
AU  - Valls Seron M
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - Man, Wing Kit
AU  - Man WK
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - Houben-Weerts, Judith H P M
AU  - Houben-Weerts JHPM
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - Tanck, Michael W T
AU  - Tanck MWT
AD  - Department of Clinical Epidemiology, Amsterdam University Medical Centres, 
      Location Academic Medical Center, University of Amsterdam, Amsterdam, The 
      Netherlands.
FAU - van Westerloo, David J
AU  - van Westerloo DJ
AD  - Intensive Care Medicine, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - van der Poll, Tom
AU  - van der Poll T
AD  - Centre of Experimental Molecular Medicine, Amsterdam University Medical Centres, 
      Location Academic Medical Center, University of Amsterdam, Amsterdam, The 
      Netherlands.
FAU - van Gool, Willem A
AU  - van Gool WA
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands.
FAU - van de Beek, Diederik
AU  - van de Beek D
AD  - Department of Neurology, Amsterdam University Medical Centres, Location Academic 
      Medical Center, Amsterdam Neuroscience, University of Amsterdam, PO Box 22660, 
      1100DD, Amsterdam, The Netherlands. d.vandebeek@amsterdamumc.nl.
LA  - eng
GR  - TOP grant #40-00812-98-10017/ZONMW_/ZonMw/Netherlands
GR  - ERC Starting Grant #281156/ERC_/European Research Council/International
PT  - Journal Article
DEP - 20220412
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha7 Nicotinic Acetylcholine Receptor)
SB  - IM
MH  - Animals
MH  - Escherichia coli/genetics
MH  - *Escherichia coli Infections/metabolism
MH  - Inflammation/metabolism
MH  - Interleukin-6/metabolism
MH  - Male
MH  - Mice
MH  - Microglia/metabolism
MH  - RNA, Messenger/metabolism
MH  - *Sepsis
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - alpha7 Nicotinic Acetylcholine Receptor/genetics/metabolism
PMC - PMC9006549
OTO - NOTNLM
OT  - Escherichia coli
OT  - Knock-out
OT  - Microglia
OT  - Microglial activation
OT  - Mouse model
OT  - Neuro-inflammation
OT  - Systemic infection
OT  - alpha7 acetylcholine receptor
OT  - alpha7nAChR
COIS- The authors do not have any competing interests.
EDAT- 2022/04/14 06:00
MHDA- 2022/04/15 06:00
PMCR- 2022/04/12
CRDT- 2022/04/13 05:07
PHST- 2021/12/23 00:00 [received]
PHST- 2022/03/29 00:00 [accepted]
PHST- 2022/04/13 05:07 [entrez]
PHST- 2022/04/14 06:00 [pubmed]
PHST- 2022/04/15 06:00 [medline]
PHST- 2022/04/12 00:00 [pmc-release]
AID - 10.1186/s12974-022-02452-8 [pii]
AID - 2452 [pii]
AID - 10.1186/s12974-022-02452-8 [doi]
PST - epublish
SO  - J Neuroinflammation. 2022 Apr 12;19(1):94. doi: 10.1186/s12974-022-02452-8.