PMID- 30123107
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 11
DP  - 2018
TI  - Regulation of IL-6 Secretion by Astrocytes via TLR4 in the Fragile X Mouse Model.
PG  - 272
LID - 10.3389/fnmol.2018.00272 [doi]
LID - 272
AB  - Fragile X syndrome (FXS) is identified by abnormal dendrite morphology and 
      altered synaptic protein expression. Astrocyte secreted factors such as Tenascin 
      C (TNC), may contribute to the synaptic changes, including maturation of the 
      synapse. TNC is a known endogenous ligand of toll-like receptor 4 (TLR4) that has 
      been shown to induce the expression of pro-inflammatory cytokines such as 
      interleukin-6 (IL-6). At the molecular level, elevated IL-6 promotes excitatory 
      synapse formation and increases dendrite spine length. With these molecular 
      changes linked to the phenotype of FXS, we examined the expression and the 
      mechanism of the endogenous TLR4 activator TNC, and its downstream target IL-6 in 
      astrocytes from the Fragile X Mental Retardation 1 (FMR1) knockout (KO) mouse 
      model. Secreted TNC and IL-6 were significantly increased in FMR1 KO astrocytes. 
      Addition of TNC and lipopolysaccharide (LPS) induced IL-6 secretion, whereas the 
      antagonist of TLR4 (LPS-RS) had an opposing effect. Cortical protein expression 
      of TNC and IL-6 were also significantly elevated in the postnatal FMR1 KO mouse. 
      In addition, there was an increase in the number of vesicular glutamate 
      transporter 1 (VGLUT1)/post synaptic density protein 95 (PSD95) positive synaptic 
      puncta of both wild-type (WT) and FMR1 KO neurons when plated with astrocyte 
      conditioned media (ACM) from FMR1 KO astrocytes, compared to those plated with 
      media from wild type astrocytes. By assessing the cellular mechanisms involved, a 
      novel therapeutic option could be made available to target abnormalities of 
      synaptic function seen in FXS.
FAU - Krasovska, Victoria
AU  - Krasovska V
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      ON, Canada.
FAU - Doering, Laurie C
AU  - Doering LC
AD  - Department of Pathology and Molecular Medicine, McMaster University, Hamilton, 
      ON, Canada.
LA  - eng
PT  - Journal Article
DEP - 20180803
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC6085486
OTO - NOTNLM
OT  - IL-6
OT  - TLR4
OT  - Tenascin C
OT  - astrocyte
OT  - development
OT  - fragile X syndrome
OT  - synapses
EDAT- 2018/08/21 06:00
MHDA- 2018/08/21 06:01
PMCR- 2018/01/01
CRDT- 2018/08/21 06:00
PHST- 2018/02/20 00:00 [received]
PHST- 2018/07/17 00:00 [accepted]
PHST- 2018/08/21 06:00 [entrez]
PHST- 2018/08/21 06:00 [pubmed]
PHST- 2018/08/21 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2018.00272 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2018 Aug 3;11:272. doi: 10.3389/fnmol.2018.00272. eCollection 
      2018.