title: Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory.
abstract: 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.
authors: Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
authors: Thiago L N
authors: TL
authors: Lazaroni
authors: Ana Cláudia S
authors: AC
authors: Raslan
authors: Walkiria R P
authors: WR
authors: Fontes
authors: Marilene L
authors: ML
authors: de Oliveira
authors: Michael
authors: M
authors: Bader
authors: Natalia
authors: N
authors: Alenina
authors: Márcio F D
authors: MF
authors: Moraes
authors: Robson A
authors: RA
authors: Dos Santos
authors: Grace S
authors: GS
authors: Pereira
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D007093:Imidazoles; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D011945:Receptors, Angiotensin; D043562:Receptors, G-Protein-Coupled; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan