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Atorvastatin prevents hippocampal cell death, neuroinflammation and oxidative stress following amyloid-β(1-40) administration in mice: evidence for dissociation between cognitive deficits and neuronal damage.
- Source :
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Experimental neurology [Exp Neurol] 2010 Dec; Vol. 226 (2), pp. 274-84. Date of Electronic Publication: 2010 Sep 15. - Publication Year :
- 2010
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Abstract
- The accumulation of amyloid-beta (Aβ) 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 Aβ(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 Aβ(1-40)-treated mice. Aβ(1-40) also induced a marked decrease in glutamatergic transporters (GLAST and GLT-1) expression and in l-[³H] glutamate uptake in mice hippocampus, in addition to spatial learning and memory deficits. Atorvastatin (10 mg/kg/day v.o.) was administered after Aβ(1-40) injection and through seven consecutive days. Atorvastatin treatment was neuroprotective against cell degeneration induced by Aβ(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 Aβ(1-40)-treated mice. These results reinforce and extend the notion of the potential neuroprotective action of atorvastatin against the neuronal toxicity induced by Aβ(1-40). In addition, the present findings suggest that the spatial learning and memory deficits induced by Aβ peptides in rodents may not be entirely related to neuronal damage.<br /> (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Transport System X-AG metabolism
Analysis of Variance
Animals
Animals, Newborn
Astrocytes drug effects
Atorvastatin
Cell Death drug effects
Cyclooxygenase 2 metabolism
Fluoresceins
Gene Expression Regulation drug effects
Glutamic Acid metabolism
Glutathione metabolism
Glutathione Peroxidase metabolism
Glutathione Reductase metabolism
Humans
In Vitro Techniques
Learning Disabilities chemically induced
Learning Disabilities drug therapy
Male
Maze Learning drug effects
Memory Disorders chemically induced
Memory Disorders drug therapy
Mice
Nerve Tissue Proteins metabolism
Organic Chemicals
Propidium
Tritium metabolism
Amyloid beta-Peptides toxicity
Encephalitis chemically induced
Encephalitis pathology
Encephalitis prevention & control
Heptanoic Acids pharmacology
Hippocampus pathology
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Neurons drug effects
Oxidative Stress drug effects
Peptide Fragments toxicity
Pyrroles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2430
- Volume :
- 226
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 20816828
- Full Text :
- https://doi.org/10.1016/j.expneurol.2010.08.030