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DOI 10.34014/2227-1848-2019-1-93-102

CHOLINERGIC SYSTEM RESPONSE TO STRESS AND DEPRESSION

 

M.Kh. Gaynutdinov1, D.M. Khakimova2, T.B. Kalinnikova1, R.R. Shagidullin1

1 Institute for Environmental Problems and Subsoil Use, Tatarstan Academy of Sciences, Kazan, Russia;

2 Kazan Federal University, Kazan, Russia

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The paper presents a summary of results considering cholinergic hypothesis on the central processes of human stress response and depression caused by chronic social stress. These studies include both the work of clinicians, who are examining pathogenesis of depression, and experiments with rodents. The authors also consider the history of stress response discovery in humans and vertebrates. The paper analyses the results of early studies (1980s-1990s), which led to the hypothesis on the key role of brain cholinergic system in nonspecific stress response of the whole multicellular organism of humans and rodents. Special attention is paid to the latest ideas on acetylcholine as the most powerful neuromodulator in the brain. Acetylcholine is said to transmit large volumes of information. The authors conducted the summary of experimental and clinical studies showing that the primary reaction of humans and rodents under stress is manifested in the activation of brain cholinergic transmission, but not in subsequent changes in serotonergic system functioning. The paper analyses numerous studies, the result of which confirmed the cholinergic hypothesis on stress and depression. These facts are as follows: firstly, the increase in the acetylcholine level in the brain or in the hippocampus (physostigmine injection) causes similar changes in the behavior and physiological state of rodents under stress; secondly, single-time stress increases the acetylcholine level in several areas of the brain, thus, correlating to adaptive changes in behavior; thirdly, chronic stress that causes disturbances in rodent behavior, which are similar to depression, is accompanied by an increase of the acetylcholine level in the brain. In general, the authors come to the conclusion that ideas on the key role of cholinergic system in stress response can serve as a scientific basis for further research on the depression mechanisms both clinically and experimentally

Keywords: stress, depression, acetylcholine, neuromodulator, behavior.

 

References

1. Koolhaas J.M., Bartolomucci A., Buwalda B., de Boer S.F., Flügge S., Korte S.M., Meerlo P., Murison R., Olivier B., Palanza P., Richter-Levin G., Sgoifo A., Steimer T., Stiedl O., van Dijk G., Wöhr M., Fuchs E. Stress revisited: A critical evaluation of the stress concept. Neurosci. Biobehav. Rev. 2011; 35 (5): 1291–1301.

2. Selye H. The stress of life. New York: McGraw-Hill; 1956. 544.

3. Selye H. Confusion and controversy in the stress field. J. Hum. Stress. 1975; 1 (2): 37–44.

4. Viner R. Putting stress in life: Hans Selye and the making of stress theory. Soc. Stud. Sci. 1999; 29 (3): 391–410.

5. Jacobson L., Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic – pituitary – adrenocortical axis. Endocr. Rev. 1991; 12 (2): 118–134.

6. De Kloet E.R., Joëls M., Holsboer F. Stress and the brain: from adaptation to disease. Nat. Rev. 2005; 6 (6): 463–475.

7. Cannon W.B. Physiological regulation of normal states: some tentative postulates concerning biological homeostatics. In: Pettit A., ed. A Chales Richet: ses amis, ses collègues, ses élèves. Paris: Édition Médicales; 1926: 91.

8. Nutt D.J. Relationship of neurotransmitters to the symptoms of major depressive disorder. J. Clin. Psychiatry. 2008; 69 (suppl. E1): 4–7.

9. Wilner P. Dopamine and depression: A review of recent evidence. I. Empirical studies. Brain. Res. Rev. 1983; 287 (3): 211–224.

10. Higley M.J., Picciotto M.R. Neuromodulation by acetylcholine: examples from schizophrenia and depression. Curr. Opin. Neurobiol. 2014; 29: 88–95.

11. Mineur Y.S., Obayemi A., Wigestrand M.B., Fote G.M., Calarco C.A., Li A.M., Picciotto M.R. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proc. Natl. Acad. Sci. USA. 2013; 110 (9): 3573–3578.

12. Picciotto M.R., Higley M.J., Mineur Y.S. Acetylcholine as neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012; 76 (1): 116–129.

13. Gilad M. The stress-induced response of the septo-hippocampal cholinergic system. A vectorial outcome of psychoneuroendocrinological interactions. Psychoneuroendocrinol. 1987; 12 (3): 167–184.

14. Janowsky D.S., El-Yosef M.K., Davis J.M., Sekerke H.J. A cholinergic-adrenergic hypothesis of mania and depression. Lancet. 1972; 2 (7778): 632–635.

15. Risch S.C., Cohen R.M., Janowsky D.S., Kalin N.H., Murphy D.L. Mood and behavioral effects of physostigmine on humans are accompanied by elevations in plasma beta-endorphin and cortisol. Science. 1980; 209 (4464): 1545–1546.

16. Hannestad J.O., Cosgrove K.P., DellaGioia N.F., Perkins E., Bois F., Bhagwagar Z., Seibyl J.P., McClure-Begley T.D., Picciotto M.R., Esterlis I. Changes in the cholinergic system between bipolar depression and euthymia as measured with [1231]5IA single photon emission computed tomography. Biol. Psychiatry. 2013; 74 (10); 768–776.

17. Saricicek A., Esterlis I., Maloney K.H., Mineur Y.S., Ruf B.M., Muralidharan A., Chen J.I., Cosgrove K.P., Kerestes R., Ghose S., Tamminga C.A., Pittman B., Bois F., Tamagnan G., Seibyl J., Picciotto M.R., Staley J.K., Bhagwagar Z. Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder. Am. J. Psychiatry. 2012; 169 (8); 851–859.

18. Mark G.P., Rada P.V., Shors T.J. Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala. Neurosci. 1996; 74 (3): 767–774.

19. Del Arco A., Segovia G., Garrido P., de Blas M., Mora F. Stress, prefrontal cortex and environmental enrichment: studies on dopamine and acetylcholine release and working memory performance in rats. Behav. Brain Res. 2007; 176 (2): 267–273.

20. Delgado P.L. Depression: the case for a monoamine deficiency. J. Clin. Psychiatry. 2000; 61 (suppl. 6): 7–11.

21. Delgado P.L., Moreno F.A. Role of norepinephrine in depression. J. Clin. Psychiatry. 2000; 61 (suppl. 1): 5–12.

22. Dunant Y., Gisiger V. Ultrafast and slow cholinergic transmission. Different involvement of acetylcholinesterase molecular forms. Molecules. 2017; 22 (8): e1300.

23. Sarter M., Parikh V., Howe W.M. Phasic acetylcholine release and the volume transmission hypothesis: time to move on. Nat. Rev. Neurosci. 2009; 10 (5): 383–390.

24. Warner-Schmidt J.L., Schmidt E.F., Marshall J.J., Rubin A.J., Arango-Lievano M., Kaplitt M.G., Ibanez-Tallon I., Heintz N., Greengard P. Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior. Proc. Natl. Acad. Sci. USA. 2012; 109 (28): 11360–1365.

25. Belujon P., Grace A.A. Hippocampus, amygdala, and stress: interacting systems that affect susceptibility to addiction. Ann. NY Acad. Sci. 2011; 1216 (1): 114–121.

26. McGaugh J.L. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Ann. Rev. Neurosci. 2004; 27 (1): 1–28.

27. Hirschfeld R.M. History and evolution of the monoamine hypothesis of depression. J. Clin. Psychiatry. 2000; 61 (Suppl. 6): 4–6.

28. Lenox R.H., Frazer A. Mechanism of action of antidepressants and mood stabilizers. In: Davis K.L., Charney D., Coyle J.T., Nemeroff C., eds. Neuropsychopharmacology: The fifth generation of progress. Philadelphia, Pennsylvania: Lippincott, Williams & Wilkins; 2002: 1139–1163.

29. Lacasse J.R., Leo J. Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS Medicine. 2005; 2 (12): e392.

 

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DOI 10.34014/2227-1848-2019-1-93-102

УДК 616.891

 

О РОЛИ ХОЛИНЕРГИЧЕСКОЙ СИСТЕМЫ В СТРЕСС-РЕАКЦИИ ОРГАНИЗМА И ДЕПРЕССИИ

 

М.Х. Гайнутдинов1, Д.М. Хакимова2, Т.Б. Калинникова1, Р.Р. Шагидуллин1

1 Институт проблем экологии и недропользования Академии наук Республики Татарстан, г. Казань, Россия;

2 ФГАОУ ВО «Казанский (Приволжский) федеральный университет», г. Казань, Россия

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В работе представлен обзор результатов исследований, в которых рассматривается холинергическая гипотеза центральных процессов стресс-реакции организма человека и депрессии, вызванной хроническими социальными стрессами. Эти исследования включают в себя как работы клиницистов, занимающихся патогенезом депрессии, так и эксперименты с грызунами. Рассмотрена история открытия стресс-реакции организмов человека и позвоночных животных. Проведен анализ результатов ранних исследований 1980–1990-х гг., которые привели к появлению гипотезы о ключевой роли холинергической системы головного мозга в реализации неспецифической стресс-реакции целого многоклеточного организма человека и грызунов. Особое внимание уделено новейшим представлениям о функционировании ацетилхолина в головном мозге в качестве нейромодулятора, осуществляющего объемный механизм передачи информации. Приведен обзор результатов экспериментальных и клинических исследований, свидетельствующих о том, что первичной реакцией организмов человека и грызунов при действии стресса является активация холинергической трансмиссии в головном мозге, а не последующие изменения функций серотонинергической системы. Проведен анализ многочисленных исследований, результатом которых явились факты, подтверждающие холинергическую гипотезу стресса и депрессии. Эти факты заключаются в следующем: во-первых, повышение уровня ацетилхолина в целом головном мозге или в гиппокампе инъекцией физостигмина и стресс вызывают сходные изменения поведения и физиологического состояния организмов грызунов; во-вторых, однократное действие стресса вызывает повышение уровня ацетилхолина в нескольких областях головного мозга, коррелирующее с адаптивными изменениями поведения; в-третьих, действие хронического стресса, вызывающего нарушения поведения грызунов, сходные с проявлениями депрессии, сопровождается повышением уровня ацетилхолина в головном мозге. В целом настоящая работа позволяет сделать вывод о том, что представления о ключевой роли холинергической системы в центральных процессах стресс-реакции могут быть научной основой дальнейших исследований механизмов депрессии
в клинике и в экспериментах.

Ключевые слова: стресс, депрессия, ацетилхолин, нейромодулятор, поведение.

 

Литература

1. Koolhaas J.M., Bartolomucci A., Buwalda B., de Boer S.F., Flügge S., Korte S.M., Meerlo P., Murison R., Olivier B., Palanza P., Richter-Levin G., Sgoifo A., Steimer T., Stiedl O., van Dijk G., Wöhr M., Fuchs E. Stress revisited: A critical evaluation of the stress concept. Neurosci. Biobehav. Rev. 2011; 35 (5): 1291–1301.

2. Selye H. The stress of life. New York: McGraw-Hill; 1956. 544.

3. Selye H. Confusion and controversy in the stress field. J. Hum. Stress. 1975; 1 (2): 37–44.

4. Viner R. Putting stress in life: Hans Selye and the making of stress theory. Soc. Stud. Sci. 1999; 29 (3): 391–410.

5. Jacobson L., Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic – pituitary – adrenocortical axis. Endocr. Rev. 1991; 12 (2): 118–134.

6. De Kloet E.R., Joëls M., Holsboer F. Stress and the brain: from adaptation to disease. Nat. Rev. 2005; 6 (6): 463–475.

7. Cannon W.B. Physiological regulation of normal states: some tentative postulates concerning biological homeostatics. In: Pettit A., ed. A Chales Richet: ses amis, ses collègues, ses élèves. Paris: Édition Médicales; 1926: 91.

8. Nutt D.J. Relationship of neurotransmitters to the symptoms of major depressive disorder. J. Clin. Psychiatry. 2008; 69 (suppl. E1): 4–7.

9. Wilner P. Dopamine and depression: A review of recent evidence. I. Empirical studies. Brain. Res. Rev. 1983; 287 (3): 211–224.

10. Higley M.J., Picciotto M.R. Neuromodulation by acetylcholine: examples from schizophrenia and depression. Curr. Opin. Neurobiol. 2014; 29: 88–95.

11. Mineur Y.S., Obayemi A., Wigestrand M.B., Fote G.M., Calarco C.A., Li A.M., Picciotto M.R. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proc. Natl. Acad. Sci. USA. 2013; 110 (9): 3573–3578.

12. Picciotto M.R., Higley M.J., Mineur Y.S. Acetylcholine as neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012; 76 (1): 116–129.

13. Gilad M. The stress-induced response of the septo-hippocampal cholinergic system. A vectorial outcome of psychoneuroendocrinological interactions. Psychoneuroendocrinol. 1987; 12 (3): 167–184.

14. Janowsky D.S., El-Yosef M.K., Davis J.M., Sekerke H.J. A cholinergic-adrenergic hypothesis of mania and depression. Lancet. 1972; 2 (7778): 632–635.

15. Risch S.C., Cohen R.M., Janowsky D.S., Kalin N.H., Murphy D.L. Mood and behavioral effects of physostigmine on humans are accompanied by elevations in plasma beta-endorphin and cortisol. Science. 1980; 209 (4464): 1545–1546.

16. Hannestad J.O., Cosgrove K.P., DellaGioia N.F., Perkins E., Bois F., Bhagwagar Z., Seibyl J.P., McClure-Begley T.D., Picciotto M.R., Esterlis I. Changes in the cholinergic system between bipolar depression and euthymia as measured with [1231]5IA single photon emission computed tomography. Biol. Psychiatry. 2013; 74 (10); 768–776.

17. Saricicek A., Esterlis I., Maloney K.H., Mineur Y.S., Ruf B.M., Muralidharan A., Chen J.I., Cosgrove K.P., Kerestes R., Ghose S., Tamminga C.A., Pittman B., Bois F., Tamagnan G., Seibyl J., Picciotto M.R., Staley J.K., Bhagwagar Z. Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder. Am. J. Psychiatry. 2012; 169 (8); 851–859.

18. Mark G.P., Rada P.V., Shors T.J. Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala. Neurosci. 1996; 74 (3): 767–774.

19. Del Arco A., Segovia G., Garrido P., de Blas M., Mora F. Stress, prefrontal cortex and environmental enrichment: studies on dopamine and acetylcholine release and working memory performance in rats. Behav. Brain Res. 2007; 176 (2): 267–273.

20. Delgado P.L. Depression: the case for a monoamine deficiency. J. Clin. Psychiatry. 2000; 61 (suppl. 6): 7–11.

21. Delgado P.L., Moreno F.A. Role of norepinephrine in depression. J. Clin. Psychiatry. 2000; 61 (suppl. 1): 5–12.

22. Dunant Y., Gisiger V. Ultrafast and slow cholinergic transmission. Different involvement of acetylcholinesterase molecular forms. Molecules. 2017; 22 (8): e1300.

23. Sarter M., Parikh V., Howe W.M. Phasic acetylcholine release and the volume transmission hypothesis: time to move on. Nat. Rev. Neurosci. 2009; 10 (5): 383–390.

24. Warner-Schmidt J.L., Schmidt E.F., Marshall J.J., Rubin A.J., Arango-Lievano M., Kaplitt M.G., Ibanez-Tallon I., Heintz N., Greengard P. Cholinergic interneurons in the nucleus accumbens regulate depression-like behavior. Proc. Natl. Acad. Sci. USA. 2012; 109 (28): 11360–1365.

25. Belujon P., Grace A.A. Hippocampus, amygdala, and stress: interacting systems that affect susceptibility to addiction. Ann. NY Acad. Sci. 2011; 1216 (1): 114–121.

26. McGaugh J.L. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Ann. Rev. Neurosci. 2004; 27 (1): 1–28.

27. Hirschfeld R.M. History and evolution of the monoamine hypothesis of depression. J. Clin. Psychiatry. 2000; 61 (Suppl. 6): 4–6.

28. Lenox R.H., Frazer A. Mechanism of action of antidepressants and mood stabilizers. In: K.L. Davis, D. Charney, J.T. Coyle, C. Nemeroff (Eds.). Neuropsychopharmacology: The fifth generation of progress. Philadelphia, Pennsylvania: Lippincott, Williams & Wilkins; 2002: 1139–1163.

29. Lacasse J.R., Leo J. Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS Medicine. 2005; 2 (12): e392.