Angiotensin-(1–7)/Mas axis integrity is required for the expression of object recognition memory

• Published in: Neurobiology of learning and memory 2012-01, Vol.97 (1), p.113-123
• Main Authors: Lazaroni, Thiago L.N., Raslan, Ana Cláudia S., Fontes, Walkiria R.P., de Oliveira, Marilene L., Bader, Michael, Alenina, Natalia, Moraes, Márcio F.D., dos Santos, Robson A., Pereira, Grace S.
• Format: Article
• Language: English
• Subjects: Angiotensin I - genetics; Angiotensin I - metabolism; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 2 Receptor Blockers - pharmacology; Angiotensin-(1–7); Animal memory; Animals; AT1 receptor; Behavioral psychophysiology; Biological and medical sciences; Brain; Fundamental and applied biological sciences. Psychology; Gene expression; Hippocampus - drug effects; Hippocampus - metabolism; Imidazoles - pharmacology; Losartan - pharmacology; Mice; Mice, Knockout; Neurobiology; Object recognition memory; Peptide Fragments - genetics; Peptide Fragments - metabolism; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Pyridines - pharmacology; Receptor Mas; Receptors, Angiotensin - metabolism; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Recognition (Psychology) - drug effects; Recognition (Psychology) - physiology; Rodents
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2011.10.003

► Ang-(1–7)/Mas axis is essential for normal ORM processing. ► Mas knockout did not affect the performance of mice in the inhibitory avoidance task. ► Blocking receptor Mas into the hippocampus impaired object recognition memory. ► Blocking of AT1, but not AT2, receptors prevents the ORM deficit of MasKo. ► MasKo has high levels of hippocampal Ang-(1–7), but not Ang I or Ang II. It has been shown that the brain has its own intrinsic renin–angiotensin system (RAS) and angiotensin-(1–7) (Ang-(1–7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1–7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1–7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1–7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1–7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1–7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1–7)/Mas axis is essential for normal ORM processing.