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Impact of genetic deletion of MrgD or Mas receptors in depressive-like behaviour in mice

Published online by Cambridge University Press:  18 August 2022

Luca Becari ,
Maria Luiza A. Fonseca ,
Sthéfanie C. A. Gonçalves ,
Michael Bader ,
Robson A. S. Santos ,
Maria José Campagnole-Santos  and
Lucas M. Kangussu Open the ORCID record for Lucas M. Kangussu [Opens in a new window]
Luca Becari
Affiliation:
Department of Morphology – Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
Maria Luiza A. Fonseca
Affiliation:
Department of Morphology – Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil Neuroscience Program, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
Sthéfanie C. A. Gonçalves
Affiliation:
Department of Physiology and Biophysics – Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
Michael Bader
Affiliation:
Max-Delbrück Center for Molecular Medicine (MDC), Berlin, Germany Institute for Biology, University of Lübeck, Lübeck, Germany Charité University Medicine Berlin, Berlin, Germany German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
Robson A. S. Santos
Affiliation:
Department of Physiology and Biophysics – Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
Maria José Campagnole-Santos
Affiliation:
Department of Physiology and Biophysics – Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
Lucas M. Kangussu*
Affiliation:
Department of Morphology – Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil Neuroscience Program, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
*
Author for correspondence: Lucas M. Kangussu, Email: lucaskangussu@ufmg.br
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Abstract

Objectives:

To evaluate the impact of genetic deletion of receptors of the counterregulatory arms of the renin–angiotensin system in depressive-like behaviours.

Methods:

8–12 weeks-old male mice wild type (WT, C57BL/6J) and mice with genetic deletion of MrgD (MrgD KO) or Mas receptors (Mas KO) were subjected to the Forced Swim Test (FST) and the Tail Suspension Test (TST). Brain-derived neurotrophic factor (BDNF) levels were measured by enzyme-linked immunosorbent assay (ELISA). Blockade of Mas was performed by acute intracerebroventricular (icv) injection of its selective antagonist, A779.

Results:

No statistical difference in immobility time was observed between MrgD KO and WT male animals subjected to FST and TST. However, acute icv injection of A779 significantly increased the immobility time of MrgD KO male mice subjected to FST and TST, suggesting the involvement of Mas in preventing depressive-like behaviour. Indeed, Mas KO male animals showed increased immobility time in FST and TST, evidencing a depressive-like behaviour in these animals, in addition to a reduction in BDNF levels in the prefrontal cortex and hippocampus. No changes in BDNF levels were observed in MrgD KO male animals.

Conclusion:

Our data showed that Mas plays an important role in the neurobiology of depression probably by modulating BDNF expression. On the contrary, lack of MrgD did not alter depressive-like behaviour, which was supported by the lack of alterations in BDNF levels.

Keywords

renin–angiotensin systemMrgDMasdepressive-like behaviourBDNF
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 35 , Issue 1 , February 2023 , pp. 27 - 34
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Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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