The effects of alamandin on cognitive functions and neuroinflammation in rat model of depression

Depression is a disease that can cause impairments in cognitive functions, including attention, memory, psychomotor functions and executive functions. Studies suggest that the renin-angiotensin system (RAS) also plays a role in the pathophysiology of major depression. Alamandin is the newest component associated with the protective axis of the RAS. The aim of our study is to determine the effects of alamandine, a new member of the RAS family, on cognitive functions, neuroinflammation and oxidative stress as a potential teropathic target in the pathophysiology of depression and related cognitive dysfunction. 35 male Sprague dawley rats, 3 months old and weighing between 300-350 g, were used. The chronic unpredictable mild stress model of depression was performed. Experimental animals divided into 5 groups of control (C), depression (D), alamandine (50 µg/kg, ip) treatment group (D+A), A779 (300 µg/kg, ip) treatment group (D+A779), both alamandine and A779 treatment group (D+ALA+A779). After the development of depression was confirmed by behavioral tests, the learning-memory performances of the animals were measured with the Morris water maze test. At the end of the experiment, prefrontal cortex, hippocampus and blood samples of the animals were isolated for biochemical studies and gene expression analyses. The sucrose preference test, open field test, elevated plus maze test, tail suspension and forced swimming tests performed to determine the anxiety levels of animals. There was a significant development of anxiety in the D group and the A779 treated group, and alamandine showed an anxiolytic effect. The time spent in the platform area significantly (p<0.001) decreased in both D and D+A779 groups compared to the controls while similar results with the control group were obtained in the alamandine-treated groups in Morris water maze test. The learning-memory markers such as hippocampal brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate (NMDA) receptor, and cAMP response element binding protein (CREB) significantly increased with alamandine treatment In addition, tumor necrosis factor alpha (TNF-α), interleukin 1β and 6, and oxidative stress markers, which are inflammatory markers that increase in parallel with the development of depression in both tissue and serum, were also significantly decreased with alamandin treatment. Based on these findings, it was concluded that alamandine has an anxiolytic effect on depression and has a positive effect on impaired spatial memory mechansim via reducing neuroinflammation and oxidative stress.