PMID- 21419111
OWN - NLM
STAT- MEDLINE
DCOM- 20110808
LR  - 20181201
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1388
DP  - 2011 May 4
TI  - Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice 
      and preserve the cytokines MCP-1 and TNF-alpha.
PG  - 32-8
LID - 10.1016/j.brainres.2011.03.024 [doi]
AB  - In contrast to cerebral cortical neurons, the extent of damage to cells of the 
      cerebellum in Alzheimer's disease (AD) is still a matter of debate. Here, we 
      examined pathological changes in the cerebellar Purkinje cells (PCs) of AD model 
      mice (amyloid precursor protein transgenic (APP-Tg) mice) at 10, 15, and 20 
      months (M) of age, and investigated the possible protective effect of two strong 
      statins (atorvastatin at 30 mg/kg/day or pitavastatin at 3mg/kg/day, p.o.) by 
      administering these statins from 5 to 20 M. The number of PCs detected by 
      hematoxylin-eosin staining in APP-Tg mice was approximately 60% of the number in 
      non-Tg mice at 10 M, and this progressively reduced with age until 20 M. 
      Moreover, the number of monocyte chemotactic protein 1 (MCP-1)-positive PCs and 
      tumor necrosis factor alpha (TNF-alpha)-positive PCs was also reduced in the 
      transgenics. In contrast, the APP-Tg mice treated with either of the two statins 
      showed a significant recovery in the number of PCs, and MCP-1 (at 20 M) and TNF-alpha 
      (at 15 and 20 M) staining in PCs was preserved. Because MCP-1 and TNF-alpha play 
      important roles in maintaining the synaptic network in PCs, the present study 
      suggests that atorvastatin and pitavastatin can maintain the number of PCs and 
      their synaptic networks in the AD cerebellum.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Kozuki, Miki
AU  - Kozuki M
AD  - Department of Neurology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 
      700-8558, Japan.
FAU - Kurata, Tomoko
AU  - Kurata T
FAU - Miyazaki, Kazunori
AU  - Miyazaki K
FAU - Morimoto, Nobutoshi
AU  - Morimoto N
FAU - Ohta, Yasuyuki
AU  - Ohta Y
FAU - Ikeda, Yoshio
AU  - Ikeda Y
FAU - Abe, Koji
AU  - Abe K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110315
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 0 (Quinolines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - A0JWA85V8F (Atorvastatin)
RN  - M5681Q5F9P (pitavastatin)
SB  - IM
MH  - Alzheimer Disease/metabolism/*pathology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Atorvastatin
MH  - Chemokine CCL2/*metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Heptanoic Acids/pharmacology
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Transgenic
MH  - Purkinje Cells/*drug effects/metabolism/*pathology
MH  - Pyrroles/pharmacology
MH  - Quinolines/pharmacology
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2011/03/23 06:00
MHDA- 2011/08/09 06:00
CRDT- 2011/03/23 06:00
PHST- 2011/02/10 00:00 [received]
PHST- 2011/03/04 00:00 [revised]
PHST- 2011/03/09 00:00 [accepted]
PHST- 2011/03/23 06:00 [entrez]
PHST- 2011/03/23 06:00 [pubmed]
PHST- 2011/08/09 06:00 [medline]
AID - S0006-8993(11)00521-X [pii]
AID - 10.1016/j.brainres.2011.03.024 [doi]
PST - ppublish
SO  - Brain Res. 2011 May 4;1388:32-8. doi: 10.1016/j.brainres.2011.03.024. Epub 2011 
      Mar 15.