Mas Knockout Mice Present Altered Behavioral and Neuroendocrine Coping Responses to Chronic Unpredictable Stress

Area of Science:

• Neuroendocrinology
• Behavioral Neuroscience
• Stress Physiology

Background:

• Chronic stress disrupts homeostasis, leading to maladaptive endocrine, behavioral, and neuropsychiatric changes.
• The renin-angiotensin system, particularly angiotensin-(1-7) acting via the Mas receptor, modulates stress responses.
• Previous research indicates Mas activation attenuates stress-induced anxiety and depression-like behaviors.

Purpose of the Study:

• To investigate the impact of genetic Mas deletion on the consequences of chronic unpredictable stress (CUS).
• To assess the role of the Mas receptor in HPA axis activity, stress-related behaviors, and neurochemical changes under chronic stress.

Main Methods:

• Mice with genetic deletion of the Mas receptor (Mas knockout, KO) were subjected to 21 days of CUS.
• Endocrine assessments included corticosterone and blood glucose measurements.
• Behavioral tests (forced swimming, elevated plus maze) and neurochemical analyses (BDNF levels) were performed.

Main Results:

• Stressed Mas KO mice showed significantly elevated corticosterone and blood glucose levels compared to stressed wild-type mice.
• Mas KO mice exhibited enhanced depression-like behavior (increased immobility) and anxiety-like behavior (reduced time in open arms).
• Reduced brain-derived neurotrophic factor (BDNF) levels were observed in key brain regions of stressed Mas KO animals.

Conclusions:

• Mas plays a critical role in the neurobiology of stress.
• Mas absence exacerbates HPA axis hyperactivity, depression- and anxiety-like behaviors, and BDNF reduction.
• These findings suggest a neuroprotective role for Mas in stress-related disorders.