ORIGINAL RESEARCH
Pathophysiology
doi: 10.25005/2074-0581-2024-26-1-57-66
EXPERIMENTAL DEPRESSION-MODULATED ACTIVATION PATTERN OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

N.A.D. RAZLAN1, M. KAPITONOVA1, R.N. ALYAUTDIN2,3, S.B. TALIP1, N. RAMLI1, T.M. NWE4

1Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia
2I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
3Scientific Center of Expertise of Medical Products, Moscow, Russian Federation
4Royal College of Medicine, UniKL, Ipoh, Malaysia

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.

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Authors' information:

Nur Amirah Diyana binti Razlan
Postgraduate Dtudent, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak
ORCID ID: 0009-0001-6515-7098
E-mail: amirah6497@gmail.com

Kapitonova Marina
MD, PhD, Professor, Professor of Anatomy, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak
Researcher ID: Y-6429-2018
Scopus ID: 8854275100
ORCID ID: 0000-0001-6055-3123
E-mail: kmarina@unimas.my

Alyautdin Renad Nikolaevich
MD, PhD, Professor of the Pharmacology Department, I.M. Sechenov First Moscow State Medical University; Head, Scientific Center for Expert Evaluation of Medicinal Products
Researcher ID: L-9261-2014
Scopus ID: 6701792451
ORCID ID: 0000-0002-4647-977X
E-mail: alyautdin@mail.ru

Talip Saiful Bahri
MD, Senior Lecturer, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak
Scopus ID: 57191838596
ORCID ID: 0000-0001-9470-4559
E-mail: tsbahri@unimas.my

Ramli Norhida
MD, Senior Lecturer, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak
Scopus ID: 56893285800
ORCID ID: 0000-0002-8764-5340
E-mail: rnorhida@unimas.my

Nwe Tin Moe
MD, PhD, Associate Professor, Royal College of Medicine, Faculty UniKL
Scopus ID: 8854275100
ORCID ID: 0000-0001-6055-3123
E-mail: mntin@unimas.my

Information about support in the form of grants, equipment, medications

The study is supported by the special top-down grant of Universiti Malaysia Sarawak F05/SpTDG/1763/2018. The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Talip Saiful Bahri,
MD Senior Lecturer, Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak

Kota Samarahan 94300, Malaysia

Tel.: +60 (198) 279003

E-mail: tsbahri@unimas.my

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