Cited by 83Renin-Angiotensin System StudiesMemory and Neural MechanismsProtein Hydrolysis and Bioactive Peptides

Inhibition of central angiotensin II enhances memory function and reduces oxidative stress status in rat hippocampus

Bild, Walther, Hritcu, Lucian, Stefanescu, Cristinel, Ciobica, Alin·2013·Progress in Neuro-Psychopharmacology and Biological Psychiatry

Abstract

While it is now well established that the independent brain renin-angiotensin system (RAS) has some important central functions besides the vascular ones, the relevance of its main bioactive peptide angiotensin II (Ang II) on the memory processes, as well as on oxidative stress status is not completely understood. The purpose of the present work was to evaluate the effects of central Ang II administration, as well as the effects of Ang II inhibition with either AT1 and AT 2 receptor specific blockers (losartan and PD-123177, respectively) or an angiotensin-converting enzyme (ACE) inhibitor (captopril). These effects were studied on the short-term memory (assessed through Y-maze) or long-term memory (as determined in passive avoidance) and on the oxidative stress status of the hippocampus. Our results demonstrate memory deficits induced by the administration of Ang II, as showed by the significant decrease of the spontaneous alternation in Y-maze (p=0.015) and latency-time in passive avoidance task (p=0.001) when compared to saline. On the other side, the administration of all the aforementioned Ang II blockers significantly improved the spontaneous alternation in Y-maze task, while losartan also increased the latency time as compared to saline in step-through passive avoidance (p=0.042). Also, increased oxidative stress status was induced in the hippocampus by the administration of Ang II, as demonstrated by increased levels of lipid peroxidation markers (malondialdehyde-MDA concentration) (p<0.0001) and a decrease in both antioxidant enzymes determined: superoxide dismutase-SOD (p<0.0001) and glutathione peroxidase-GPX (p=0.01), as compared to saline. Additionally, the administration of captopril resulted in an increase of both antioxidant enzymes and decreased levels of lipid peroxidation (p=0.001), while PD-123177 significantly decreased MDA concentration (p>0.0001) vs. saline. Moreover, significant correlations were found between all of the memory related behavioral parameters and the main oxidative stress markers from the hippocampus, which is known for its implication in the processes of memory and also where RAS components are well expressed. This could be relevant for the complex interactions between Ang II, behavioral processes and neuronal oxidative stress, and could generate important therapeutic approaches.

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Crossref · 10.1016/j.pnpbp.2012.12.009

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Authors
Bild, W., Hritcu, L., Stefanescu, C., & Ciobica, A.
Affiliations
  • Grigore T. Popa University of Medicine and Pharmacy (RO)
  • Alexandru Ioan Cuza University (RO)
Corresponding author
Ciobica, Alin
Venue
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher
Elsevier BV
Published
2013-06
Volume
43
Pages
79-88
ISSN
0278-5846 (ISSN-L)
OpenAlex
W2091505284
Cited by
83
References
108
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 10 · 2013: 6
FWCI
5.35
Type
journal article
Language
en
Open access
closed
Locations
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
POSDRU (/89/1.5/S/49944)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Hydrolysis and Bioactive Peptides
Keywords
angiotensin II, central renin-angiotensin system, memory, hippocampus, oxidative stress, losartan, captopril, angiotensin II type 1 receptor, angiotensin II type 2 receptor, lipid peroxidation, malondialdehyde, superoxide dismutase, glutathione peroxidase, spatial memory, passive avoidance, spontaneous alternation
MeSH terms
Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Animals, Avoidance Learning, Behavior, Animal, Captopril, Glutathione Peroxidase, Hippocampus, Imidazoles, Male, Malondialdehyde, Memory, Memory, Short-Term, Psychomotor Performance, Pyridines, Superoxide Dismutase, Lipid Peroxidation, Rats, Wistar, Oxidative Stress, Maze Learning, Losartan, Angiotensin II Type 1 Receptor Blockers, Rats, Angiotensin Receptor Antagonists, Angiotensin II Type 2 Receptor Blockers

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