PMID- 20558576
OWN - NLM
STAT- MEDLINE
DCOM- 20110125
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 177
IP  - 2
DP  - 2010 Aug
TI  - Long-term expression of tissue-inhibitor of matrix metalloproteinase-1 in the 
      murine central nervous system does not alter the morphological and behavioral 
      phenotype but alleviates the course of experimental allergic encephalomyelitis.
PG  - 840-53
LID - 10.2353/ajpath.2010.090918 [doi]
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are a family of closely related 
      proteins that inhibit matrix metalloproteinases (MMPs). In the central nervous 
      system (CNS), TIMPs 2, 3, and 4 are constitutively expressed at high levels, 
      whereas TIMP1 can be induced by various stimuli. Here, we studied the effects of 
      constitutive expression of TIMP1 in the CNS in transgenic mice. Transgene 
      expression started prenatally and persisted throughout lifetime at high levels. 
      Since MMP activity has been implicated in CNS development, in proper function of 
      the adult CNS, and in inflammatory disorders, we investigated Timp1-induced CNS 
      alterations. Despite sufficient MMP inhibition, high expressor transgenic mice 
      had a normal phenotype. The absence of compensatory up-regulation of MMP genes in 
      the CNS of Timp1 transgenic mice indicates that development, learning, and memory 
      functions do not require the entire MMP arsenal. To elucidate the effects of 
      strong Timp1 expression in CNS inflammation, we induced experimental allergic 
      encephalomyelitis. We observed a Timp1 dose-dependent mitigation of both 
      experimental allergic encephalomyelitis symptoms and histological lesions in the 
      CNS of transgenic mice. All in all, our data demonstrate that (1) long-term CNS 
      expression of TIMP1 with complete suppression of gelatinolytic activity does not 
      interfere with physiological brain function and (2) TIMP1 might constitute a 
      promising candidate for long-term therapeutic treatment of inflammatory CNS 
      diseases such as multiple sclerosis.
FAU - Althoff, Gioia E M
AU  - Althoff GE
AD  - Department of Neuropathology, University of Marburg, Marburg, Germany.
FAU - Wolfer, David P
AU  - Wolfer DP
FAU - Timmesfeld, Nina
AU  - Timmesfeld N
FAU - Kanzler, Benoit
AU  - Kanzler B
FAU - Schrewe, Heinrich
AU  - Schrewe H
FAU - Pagenstecher, Axel
AU  - Pagenstecher A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100617
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Central Nervous System/*metabolism/pathology
MH  - Encephalomyelitis, Autoimmune, Experimental/*metabolism
MH  - Female
MH  - Male
MH  - Matrix Metalloproteinases/genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Neuropsychological Tests
MH  - Pregnancy
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics/*metabolism
PMC - PMC2913353
EDAT- 2010/06/19 06:00
MHDA- 2011/01/28 06:00
PMCR- 2011/08/01
CRDT- 2010/06/19 06:00
PHST- 2010/06/19 06:00 [entrez]
PHST- 2010/06/19 06:00 [pubmed]
PHST- 2011/01/28 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - S0002-9440(10)60140-X [pii]
AID - 10.2353/ajpath.2010.090918 [doi]
PST - ppublish
SO  - Am J Pathol. 2010 Aug;177(2):840-53. doi: 10.2353/ajpath.2010.090918. Epub 2010 
      Jun 17.