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
Authors: Gianni Mancini
Andreza F de Bem
Sarah C Bezerra
Tetsadê C B Piermartiri
Filipe S Duarte
Daniel Rial
Carla I Tasca
Cláudia P Figueiredo
Rui D S Prediger
Journal: Experimental Neurology (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: amyloid-beta peptides; glial cells; neuroinflammatory; oxidative responses; cognitive deficits
Affiliations: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis, SC, Brazil.

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. 

Retracted: No

PubPeer comments:
 Figure 3A: More similar than expected ![file] Figure 5A and 5B: More similar than expected. Could authors check please? ![file] , 
 We have examined the Figures, and we agree that the highlighted panels are duplicated. We would like to thank this attentive researcher for identifying this error and bringing it to our attention. We also would like to sincerely apologize to the Experimental Neurology editorial team, reviewers, and other scientific community members for the inconvenience caused by our unintended oversight. We would like to emphasize that our editorial mistake does not alter the study s conclusion, and we are confident about the integrity of our work. Please note that Figures 3 and 5 simply display images selected to represent the overall group quantitative data presented in these figures. We are currently attempting to retrieve the original data to correct the figure, and we are in contact with the Experimental Neurology editorial team to provide an Errata to the paper. Sincerely, , 
 Corrigendum to u201cAtorvastatin prevents hippocampal cell death, neuroinflammation and oxidative stress following amyloid-u03b21u201340 administration in mice: Evidence for dissociation between cognitive deficits and neuronal damageu201d: [Experimental Neurology, 226:2 (2010) 274u2013284] https: www.sciencedirect.com science article pii S001448862100248X?via%3Dihub The authors regret that in the originally published version of this manuscript two inaccuracies were noted and listed in this corrigendum: The hippocampal image shown in panel 3A was inadvertently replicated when the final Fig. 3 was prepared for publication. We have amended this error and now provide the correct representative image of GFAP immunostaining from group Au03b21u201340 treated with saline. Similarly, in Fig. 5B the representative image of hippocampal GLT-1 was also inadvertently replicated in the panel showing GLAST immunostaining (Fig. 5A). We have amended this error and now provide the correct representative image of GLAST immunostaining from group Au03b21u201340 treated with saline. This issue did not affect the quantitative analysis of the data and corresponding statistics presented in panels C and D of Fig. 3, Fig. 5, and thus did not affect the conclusions of our study. The authors would like to apologize for any inconvenience caused. ,