PMID- 24594387
OWN - NLM
STAT- MEDLINE
DCOM- 20141208
LR  - 20171116
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 38
DP  - 2014 May
TI  - Matrix metalloproteinase-3 is a possible mediator of neurodevelopmental 
      impairment due to polyI:C-induced innate immune activation of astrocytes.
PG  - 272-82
LID - S0889-1591(14)00060-9 [pii]
LID - 10.1016/j.bbi.2014.02.014 [doi]
AB  - Increasing epidemiological evidence indicates that prenatal infection and 
      childhood central nervous system infection with various viral pathogens enhance 
      the risk for several neuropsychiatric disorders. 
      Polyriboinosinic-polyribocytidilic acid (polyI:C) is known to induce strong 
      innate immune responses that mimic immune activation by viral infections. Our 
      previous findings suggested that activation of the innate immune system in 
      astrocytes results in impairments of neurite outgrowth and spine formation, which 
      lead to behavioral abnormalities in adulthood. To identify candidates of 
      astrocyte-derived humoral factors that affect neuronal development, we analyzed 
      astrocyte-conditioned medium (ACM) from murine astrocyte cultures treated with 
      polyI:C (polyI:C-ACM) by two-dimensional fluorescence difference gel 
      electrophoresis (2D-DIGE). Through a quantitative proteomic screen, we found that 
      13 protein spots were differentially expressed compared with ACM from 
      vehicle-treated astrocytes (control-ACM), and characterized one of the 
      candidates, matrix metalloproteinase-3 (Mmp3). PolyI:C treatment significantly 
      increased the expression levels of Mmp3 mRNA and protein in astrocytes, but not 
      microglia. PolyI:C-ACM was associated with significantly higher Mmp3 protein 
      level and enzyme activity than control-ACM. The addition of recombinant Mmp3 into 
      control-ACM impaired dendritic elongation of primary cultured hippocampal 
      neurons, while the deleterious effect of polyI:C-ACM on neurite elongation was 
      attenuated by knockdown of Mmp3 in astrocytes. These results suggest that Mmp3 is 
      a possible mediator of polyI:C-ACM-induced neurodevelopmental impairment.
CI  - Copyright (c) 2014. Published by Elsevier Inc.
FAU - Yamada, Shinnosuke
AU  - Yamada S
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, Nagoya 466-8560, Japan.
FAU - Nagai, Taku
AU  - Nagai T
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, Nagoya 466-8560, Japan.
FAU - Nakai, Tsuyoshi
AU  - Nakai T
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, Nagoya 466-8560, Japan.
FAU - Ibi, Daisuke
AU  - Ibi D
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, Nagoya 466-8560, Japan.
FAU - Nakajima, Akira
AU  - Nakajima A
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, Nagoya 466-8560, Japan.
FAU - Yamada, Kiyofumi
AU  - Yamada K
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, Nagoya 466-8560, Japan. Electronic address: 
      kyamada@med.nagoya-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140301
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/enzymology/*immunology/metabolism
MH  - Cells, Cultured
MH  - *Immunity, Innate
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/drug effects/metabolism
MH  - Poly I-C/pharmacology
MH  - Up-Regulation
OTO - NOTNLM
OT  - Astrocyte
OT  - Cytokine
OT  - Immune response
OT  - Mmp3
OT  - Neuron
OT  - Neuron-glia interactions
OT  - PolyI:C
OT  - Schizophrenia
OT  - Secretome
OT  - Viral infection
EDAT- 2014/03/07 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/03/06 06:00
PHST- 2013/12/05 00:00 [received]
PHST- 2014/02/13 00:00 [revised]
PHST- 2014/02/24 00:00 [accepted]
PHST- 2014/03/06 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0889-1591(14)00060-9 [pii]
AID - 10.1016/j.bbi.2014.02.014 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2014 May;38:272-82. doi: 10.1016/j.bbi.2014.02.014. Epub 2014 
      Mar 1.