Post-stress changes in il-6 and bdnf mRNA levels in the hippocampus and blood of rats with a genetically determined contrast level of nervous system excitability

Neuroinflammation is considered as one of the mechanisms by which stress can potentially lead to a disturbance of the functions of the central nervous system. The presence of neuroimmune dysfunction after stress, and what genetic factors increase the risk of post-stress neuroinflammation has not been sufficiently investigated. Genetically determined excitability of the nervous system is a promising marker of individual vulnerability to stress, manifested in post-stress disorders associated with the specifics of the formation of neuroinflammation.

The aim of this work was to study post-stress changes in the expression of pro-inflammatory il-6 genes in the blood and hippocampus and anti-inflammatory cytokine bdnf in the blood of rats with genetically determined high and low levels of excitability of the nervous system. Breeding animals were used, males of two strains of rats aged 5 months: with a high threshold (HT) of excitability of the nervous system (low excitable) and a low threshold (LT) of excitability of the nervous system (high excitable) from the biological collection of the Pavlov Institute of Physiology of the Russian Academy of Sciences. The stress model is a long-term emotional and painful stress according to the scheme of K. Hecht. Experimental and control animals were decapitated 24 hours, 7 days and 24 days after the end of stress exposure. Changes in the mRNA level of the il-6 and bdnf genes were evaluated using real-time PCR.

Chronic stress led to a significant increase in the level of il-6 mRNA in the hippocampus only in high excitable animals 24 days after the end of stress. In the blood, the mRNA level of this cytokine increased only in low-excitable rats. The expression of the bdnf gene in blood did not change in response to stress in any of the strains.

1. Fenster RJ, et al. Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man. Nature Reviews Neuroscience. 2018;19(9):535–551.

2. Dantzer R. Neuroimmune interactions: from the brain to the immune system and vice versa. Physiol Rev. 2018;98(1): 477–504.

3. Erta M, Quintana A, Hidalgo J. Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci. 2012;8:1254–1266.

4. Thakkar, B, Acevedo EO. BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges. Brain and Behavior. 2023;13(е2903). DOI: 10.1002/brb3.2903

5. Rossini PM, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an IFCN Committee. Clin. Neurophysiol. 2015;126(6):1071–1107.

6. Павлов ИП. Лекции о работе больших полушарий головного мозга. М.: Юрайт. 2024. 362 с.

7. Сиваченко ИБ, и др. Импульсная активность и нестабильность генома нейронов миндалевидного комплекса у крыс селектированных линий с контрастной возбудимостью нервной системы в нормальных и стрессовых условиях. Журнал высшей нервной деятельности им. И.П. Павлова. 2020;70(5):655–667.

8. Вайдо АИ, Ширяева НВ, Павлова М. Б. и др. Селектированные линии крыс с высоким и низким порогом возбудимости: модель для изучения дезадаптивных состояний, зависимых от уровня возбудимости нервной системы. Лабораторные животные для научных исследований. 2018;3:12–22.

9. Вайдо АИ, Дюжикова НА, Ширяева НВ и др. Системный контроль молекулярно-клеточных и эпигенетических механизмов долгосрочных последствий стресса. Генетика. 2009;45(3):342–348.

10. Shalaginova IG, Tuchina OP, Turkin AV, Vylegzhanina AE, Nagumanova AN, Zachepilo TG, et al. The Effect of Long-Term Emotional and Painful Stress on the Expression of Proinflammatory Cytokine Genes in Rats with High and Low Excitability of the Nervous System. J Evol Biochem Physiol. 2023;59(2):642–652. DOI: 10.1134/S0022093023020291

11. Khan A, Geiger L, Czéh B. Stress-Induced Morphological, Cellular and Molecular Changes in the Brain-Lessons Learned from the Chronic Mild Stress Model of Depression. Cells. 2020;9. DOI: 10.3390/cells9041026

12. Sorrells SF, Sapolsky RM. An inflammatory review of glucocorticoid actions in the CNS. Brain. Behav. Immun. 2007;21(3):259–272.

13. Шалагинова ИГ, Зачепило ТГ, Дюжикова НА. Влияние длительного эмоционально-болевого стрессорного воздействия на экспрессию гена bdnf в мозге крыс с контрастной возбудимостью нервной системы. Медицинский академический журнал. 2023;23(1):67–74. DOI: 10.17816/MAJ119980