PMID- 22269142
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20161125
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 418
IP  - 2
DP  - 2012 Feb 10
TI  - Replacement of microglial cells using Clodronate liposome and bone marrow 
      transplantation in the central nervous system of SOD1(G93A) transgenic mice as an 
      in vivo model of amyotrophic lateral sclerosis.
PG  - 359-65
LID - 10.1016/j.bbrc.2012.01.026 [doi]
AB  - Disease progression of amyotrophic lateral sclerosis (ALS) is partially mediated 
      by the toxic microenvironment established by microglia. In the present study, we 
      used SOD1G93A transgenic mice as an in vivo ALS model and replaced microglia 
      expressing mutant SOD1 (mSOD1) with microglia expressing wild-type SOD1 (w/tSOD1) 
      to modulate the toxic microenvironment. Stereotactic injection of Clodronate 
      liposome, a selective toxin against the monocyte/macrophage system, into the 
      fourth ventricle of the brains of 12-week-old asymptomatic ALS mice reduced the 
      number of microglia effectively in the central nervous system. Subsequent bone 
      marrow transplantation (BMT) with bone marrow cells (BMCs) expressing w/tSOD1 and 
      GFP leads to replacement of the endogenous microglia of the ALS mice with 
      microglia expressing w/tSOD1 and GFP. The expression of mSOD1 in the other neural 
      cells was not influenced by the replacement procedures, and immunological side 
      effects were not observed. The replacement of microglia significantly slowed 
      disease progression and prolonged survival of the ALS mice compared with the ALS 
      mice treated by stereotactic injection of PBS-liposome and BMT with BMCs 
      expressing mSOD1 or w/tSOD1. These results suggest that replacement of microglia 
      would improve the neural cell microenvironment, thereby slowing disease 
      progression. The mechanisms and functional implications of this replacement 
      require further elucidation.
CI  - Crown Copyright (c) 2012. Published by Elsevier Inc. All rights reserved.
FAU - Lee, Jae Chul
AU  - Lee JC
AD  - Department of Anatomy, Seoul National University College of Medicine, 28 
      Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea.
FAU - Seong, Jinsil
AU  - Seong J
FAU - Kim, Seung Hyun
AU  - Kim SH
FAU - Lee, Se Jeong
AU  - Lee SJ
FAU - Cho, Yu Jin
AU  - Cho YJ
FAU - An, Jaeyeol
AU  - An J
FAU - Nam, Do-Hyun
AU  - Nam DH
FAU - Joo, Kyeung Min
AU  - Joo KM
FAU - Cha, Choong Ik
AU  - Cha CI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120117
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Liposomes)
RN  - 0813BZ6866 (Clodronic Acid)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/genetics/pathology/*therapy
MH  - Animals
MH  - *Bone Marrow Transplantation
MH  - Central Nervous System/*enzymology/pathology
MH  - Clodronic Acid/*administration & dosage
MH  - Disease Models, Animal
MH  - Injections, Intraventricular
MH  - Liposomes
MH  - Mice
MH  - Mice, Transgenic
MH  - Microglia/drug effects/*enzymology/pathology
MH  - Mutation
MH  - Superoxide Dismutase/*biosynthesis/genetics
MH  - Superoxide Dismutase-1
EDAT- 2012/01/25 06:00
MHDA- 2012/04/10 06:00
CRDT- 2012/01/25 06:00
PHST- 2012/01/04 00:00 [received]
PHST- 2012/01/06 00:00 [accepted]
PHST- 2012/01/25 06:00 [entrez]
PHST- 2012/01/25 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
AID - S0006-291X(12)00049-6 [pii]
AID - 10.1016/j.bbrc.2012.01.026 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Feb 10;418(2):359-65. doi: 
      10.1016/j.bbrc.2012.01.026. Epub 2012 Jan 17.