PMID- 20816828
OWN - NLM
STAT- MEDLINE
DCOM- 20101112
LR  - 20220321
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 226
IP  - 2
DP  - 2010 Dec
TI  - Atorvastatin prevents hippocampal cell death, neuroinflammation and oxidative 
      stress following amyloid-beta(1-40) administration in mice: evidence for 
      dissociation between cognitive deficits and neuronal damage.
PG  - 274-84
LID - 10.1016/j.expneurol.2010.08.030 [doi]
AB  - The accumulation of amyloid-beta (Abeta) peptides in the brain of human and rodents 
      has been associated with the activation of glial cells, neuroinflammatory and 
      oxidative responses, and cognitive deficits. These oxidative changes leave 
      glutamate transporters more vulnerable and may result in reduction of their 
      functions, resulting in excitotoxic damage. Herein, we evaluated the effects of 
      atorvastatin, a HMG-CoA reductase inhibitor, in molecular and behavioral 
      alterations induced by a single intracerebroventricular injection of aggregated 
      Abeta(1-40) (400 pmol) in mice. An increased glial fibrillar acidic protein (GFAP) 
      expression and cyclooxygenase-2 (COX-2) levels, as well as increased lipid 
      peroxidation and impairment in the glutathione antioxidant system and cell 
      degeneration was found in the hippocampus of Abeta(1-40)-treated mice. Abeta(1-40) also 
      induced a marked decrease in glutamatergic transporters (GLAST and GLT-1) 
      expression and in l-[(3)H] glutamate uptake in mice hippocampus, in addition to 
      spatial learning and memory deficits. Atorvastatin (10 mg/kg/day v.o.) was 
      administered after Abeta(1-40) injection and through seven consecutive days. 
      Atorvastatin treatment was neuroprotective against cell degeneration induced by 
      Abeta(1-40), reducing inflammatory and oxidative responses and increasing the 
      expression of glutamatergic transporters. On the other hand, atorvastatin did not 
      reverse the cognitive impairments and failed to alter the hippocampal glutamate 
      uptake in Abeta(1-40)-treated mice. These results reinforce and extend the notion of 
      the potential neuroprotective action of atorvastatin against the neuronal 
      toxicity induced by Abeta(1-40). In addition, the present findings suggest that the 
      spatial learning and memory deficits induced by Abeta peptides in rodents may not be 
      entirely related to neuronal damage.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Piermartiri, Tetsade C B
AU  - Piermartiri TC
AD  - Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal 
      de Santa Catarina, Trindade, 88040-900 Florianopolis, SC, Brazil.
FAU - Figueiredo, Claudia P
AU  - Figueiredo CP
FAU - Rial, Daniel
AU  - Rial D
FAU - Duarte, Filipe S
AU  - Duarte FS
FAU - Bezerra, Sarah C
AU  - Bezerra SC
FAU - Mancini, Gianni
AU  - Mancini G
FAU - de Bem, Andreza F
AU  - de Bem AF
FAU - Prediger, Rui D S
AU  - Prediger RD
FAU - Tasca, Carla I
AU  - Tasca CI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100915
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Fluoresceins)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Organic Chemicals)
RN  - 0 (Peptide Fragments)
RN  - 0 (Pyrroles)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 0 (fluoro jade)
RN  - 10028-17-8 (Tritium)
RN  - 36015-30-2 (Propidium)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.8.1.7 (Glutathione Reductase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
EIN - Exp Neurol. 2021 Nov;345:113840. PMID: 34417015
MH  - Amino Acid Transport System X-AG/metabolism
MH  - Amyloid beta-Peptides/*toxicity
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/drug effects
MH  - Atorvastatin
MH  - Cell Death/drug effects
MH  - Cyclooxygenase 2/metabolism
MH  - *Encephalitis/chemically induced/pathology/prevention & control
MH  - Fluoresceins
MH  - Gene Expression Regulation/drug effects
MH  - Glutamic Acid/metabolism
MH  - Glutathione/metabolism
MH  - Glutathione Peroxidase/metabolism
MH  - Glutathione Reductase/metabolism
MH  - Heptanoic Acids/*pharmacology
MH  - Hippocampus/*pathology
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - In Vitro Techniques
MH  - Learning Disabilities/chemically induced/drug therapy
MH  - Male
MH  - Maze Learning/drug effects
MH  - Memory Disorders/chemically induced/drug therapy
MH  - Mice
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/*drug effects
MH  - Organic Chemicals
MH  - Oxidative Stress/*drug effects
MH  - Peptide Fragments/*toxicity
MH  - Propidium
MH  - Pyrroles/*pharmacology
MH  - Tritium/metabolism
EDAT- 2010/09/08 06:00
MHDA- 2010/11/13 06:00
CRDT- 2010/09/07 06:00
PHST- 2010/02/01 00:00 [received]
PHST- 2010/08/24 00:00 [revised]
PHST- 2010/08/26 00:00 [accepted]
PHST- 2010/09/07 06:00 [entrez]
PHST- 2010/09/08 06:00 [pubmed]
PHST- 2010/11/13 06:00 [medline]
AID - S0014-4886(10)00329-8 [pii]
AID - 10.1016/j.expneurol.2010.08.030 [doi]
PST - ppublish
SO  - Exp Neurol. 2010 Dec;226(2):274-84. doi: 10.1016/j.expneurol.2010.08.030. Epub 
      2010 Sep 15.