PMID- 21955601
OWN - NLM
STAT- MEDLINE
DCOM- 20120227
LR  - 20181201
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 197
DP  - 2011 Dec 1
TI  - Progressive neurovascular disturbances in the cerebral cortex of Alzheimer's 
      disease-model mice: protection by atorvastatin and pitavastatin.
PG  - 358-68
LID - 10.1016/j.neuroscience.2011.09.030 [doi]
AB  - Structural and functional abnormalities in the neurovascular unit (NVU) have been 
      recently observed in Alzheimer's disease (AD). Statins, which are used clinically 
      for reducing cholesterol levels, can also exert beneficial vascular actions. 
      Thus, we examined the protective effects of statins on NVU disturbances in a 
      mouse AD model. Amyloid precursor protein (APP) transgenic (Tg) mice were used as 
      a model of AD. Atorvastatin (30 mg/kg/day, p.o.) or pitavastatin (3 mg/kg/day, 
      p.o.) were administered from 5 to 20 months of age. Changes in the NVU, including 
      the endothelium and basement membrane, as well as astrogliosis and matrix 
      metalloproteinase-9 (MMP-9) activation, were assessed. There was a reduction in 
      immunopositive staining for N-acetyl glucosamine oligomer (NAGO) in the 
      endothelium and in collagen IV in the APP vehicle (APP/Ve) group, with collagen 
      IV staining most weakest near senile plaques (SPs). There was also an increase in 
      intensity and number of glial fibrillary acidic protein (GFAP)-positive 
      astrocytes, particularly around the SP, where MMP-9 was more strongly labeled. 
      Double immunofluorescent analysis showed that astrocytic endfeet had detached 
      from the capillary endothelium in the APP/Ve group. Treatment with atorvastatin 
      or pitavastatin ameliorated the activation of MMP-9. Overall, these data suggest 
      that statins may have therapeutic potential for AD by protecting NVU.
CI  - Copyright A(c) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Kurata, T
AU  - Kurata T
AD  - Department of Neurology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 
      700-8558, Japan.
FAU - Miyazaki, K
AU  - Miyazaki K
FAU - Kozuki, M
AU  - Kozuki M
FAU - Morimoto, N
AU  - Morimoto N
FAU - Ohta, Y
AU  - Ohta Y
FAU - Ikeda, Y
AU  - Ikeda Y
FAU - Abe, K
AU  - Abe K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110919
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Pyrroles)
RN  - 0 (Quinolines)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - M5681Q5F9P (pitavastatin)
SB  - IM
MH  - Alzheimer Disease/*physiopathology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Atorvastatin
MH  - Blotting, Western
MH  - Cerebral Cortex/blood supply/*physiopathology
MH  - Cerebrovascular Circulation/*drug effects
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/drug effects
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Heptanoic Acids/*pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Neuroprotective Agents/*pharmacology
MH  - Pyrroles/*pharmacology
MH  - Quinolines/*pharmacology
EDAT- 2011/10/01 06:00
MHDA- 2012/03/01 06:00
CRDT- 2011/09/30 06:00
PHST- 2011/06/17 00:00 [received]
PHST- 2011/09/08 00:00 [revised]
PHST- 2011/09/14 00:00 [accepted]
PHST- 2011/09/30 06:00 [entrez]
PHST- 2011/10/01 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
AID - S0306-4522(11)01084-0 [pii]
AID - 10.1016/j.neuroscience.2011.09.030 [doi]
PST - ppublish
SO  - Neuroscience. 2011 Dec 1;197:358-68. doi: 10.1016/j.neuroscience.2011.09.030. 
      Epub 2011 Sep 19.