EXPERIMENTAL DEPRESSION-MODULATED ACTIVATION PATTERN OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS
Authors:   Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia, RAZLAN N.A.D. , KAPITONOVA M. ,   Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia, ALYAUTDIN R.N. ,   I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation,   Scientific Center of Expertise of Medical Products, Moscow, Russian Federation, TALIP S.B. ,   Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia, RAMLI N. ,   Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia, NWE T.M. ,   Royal College of Medicine, UniKL, Ipoh, Malaysia
Published: March 2024

Objective: To study the effect of modelled depression not associated with stress on the hypothalamic-pituitary-adrenal system (HPAS) in mice. Methods: The experiment was conducted on the twenty-four C57BL/6 mice weighing 20-25 g, divided into two groups: an experimental one, involving animals with reserpine-induced depression, and a control one, the animals of which were administered normal saline instead of reserpine solution. At the end of the experiment, behavioral tests were performed (open field, sucrose preference, forced swimming), and the corticosterone concentration in blood was measured using ELISA. Image analysis of histological changes in the adrenal gland and thymus was performed. All results were statistically processed using SPSS 27.0.1 software, with p<0.05 indicating the significance of differences. Results: Animals of the experimental group showed a significantly higher level of corticosterone in the blood (p<0.01), significant changes in behavior in the open field test (distance traveled, rearing, frequency of urination and defecation, p<0.01), reduced sucrose preference (p<0.01) and shortened duration of the active phase in the forced swimming test (p<0.01) than the animals of the control group. Besides, in the mice of the experimental group, a significant increase in the volume density of the zona fasciculata of the adrenal cortex was found (p<0.05), as well as the area of its spongiocytes and their nuclei (p<0.05). In the thymus of the experimental animals, a significant decrease in the cortex-medulla ratio was noted (p<0.05); and an increase in the volume density of tingible body macrophages (p<0.05) compared to the control group of mice. Conclusion: Modelled depression, not associated with stress, the depth of which was assessed by behavioral tests, caused activation of the HPAS, manifested by increased corticosterone levels, hyperplasia of the zona fasciculata of the adrenal cortex, hypertrophy of its spongiocytes and their nuclei, as well as changes in the thymus, indicating associated immunosuppression. Thus, the study showed that, along with the well-known phenomenon of the development of depression against the background of chronic stress-associated activation of HPAS, there is an inverse mechanism leading to activation of the HPAS during the development of depression not associated with stress, which must be taken into account when developing the new strategies of treating depression. Keywords: Depression, hypothalamic-pituitary-adrenal system, corticosterone, immune system, mice.