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

Acta Neuropsychiatr. 2022 Aug 18:1-24. doi: 10.1017/neu.2022.20. Online ahead of print.


OBJECTIVES: To evaluate the impact of genetic deletion of receptors of the counterregulatory arms of the renin-angiotensin system in depressive-like behaviors.

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 depression-like behavior. Indeed, Mas KO male animals showed increased immobility time in FST and TST, evidencing a depressive-like behavior 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 behavior, which was supported by the lack of alterations in BDNF levels.

PMID:35979816 | DOI:10.1017/neu.2022.20

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