Activation of angiotensin-converting enzyme 2 produces an antidepressant-like effect via MAS receptors in mice

Molecular Brain

Research

Koichi Tan-No¹  Osamu Nakagawasai¹  Wataru Nemoto¹  Ryota Yamagata¹  Taisei Koyama¹  Kohei Takahashi² 

[1] Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, 981-8558, Sendai, Miyagi, Japan;Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, 981-8558, Sendai, Miyagi, Japan;Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, 324-8501, Ohtawara, Tochigi, Japan;

关键词: Antidepressant;    Angiotensin-converting enzyme 2;    Ang (1–7);    Diminazene;    MAS receptor;   

DOI  :  10.1186/s13041-023-01040-y

 received in 2023-03-29, accepted in 2023-05-29,  发布年份 2023

来源: Springer

【 摘 要 】

Angiotensin (Ang)-converting-enzyme (ACE) 2 converts Ang II into Ang (1–7), which in turn acts on MAS receptors (ACE2/Ang (1–7)/MAS receptors pathway). This pathway has neuroprotective properties, making it a potential therapeutic target for psychiatric disorders such as depression. Thus, we examined the effects of diminazene aceturate (DIZE), an ACE2 activator, on depressive-like behavior using behavioral, pharmacological, and biochemical assays. To determine whether DIZE or Ang (1–7) produce antidepressant-like effects, we measured the duration of immobility of mice in the tail suspension test following their intracerebroventricular administration. Next, we measured the levels of ACE2 activation in the cerebral cortex, prefrontal cortex, hippocampus, and amygdala after DIZE injection, and examined which cell types, including neurons, microglia, and astrocytes, express ACE2 in the hippocampus using immunofluorescence. Administration of DIZE or Ang (1–7) significantly shortened the duration of immobility time in the tail suspension test, while this effect was inhibited by the co-administration of the MAS receptor antagonist A779. DIZE activated ACE2 in the hippocampus. ACE2 was localized to neurons, astrocytes, and microglia in the hippocampus. In conclusion, these results suggest that DIZE may act on ACE2-positive cells in the hippocampus where it increases the activity of ACE2, thereby enhancing signaling of the ACE2/Ang (1–7)/MAS receptor pathway and resulting in antidepressant-like effects.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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