Скачать статью

DOI: 10.23648/UMBJ.2018.29.11371

УДК 612.826.4

РОЛЬ АРГИНИН-ВАЗОПРЕССИНА В РЕГУЛЯЦИИ ФУНКЦИИ ЦИРКАДИАННЫХ БИОЛОГИЧЕСКИХ ЧАСОВ СУПРАХАРИЗМАТИЧЕСКОГО ЯДРА ГИПОТАЛАМУСА

М.А. Ткачева, Е.М. Инюшкина, С.Д. Карян, А.Н. Инюшкин

ФГАОУ ВО «Самарский национальный исследовательский университет им. академика С.П. Королева», г. Самара, Россия

e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Аргинин-вазопрессин является наиболее распространенным нейропептидом в нейронах супрахиазматического ядра млекопитающих, выполняющим роль главного циркадианного осциллятора. Существует суточный ритм количества вазопрессинергических нейронов в супрахиазматическом ядре с ростом в дневные часы и увеличением продукции вазопрессина в утренние часы. Этот ритм важен для циклической суточной регуляции активности гормональных гипоталамо-гипофизарно-надпочечниковой и гипоталамо-гипофизарно-гонадальной осей, а также тонуса вегетативной нервной системы. Вазопрессинергические нейроны супрахиазматического ядра оказались вовлеченными в патогенез ряда заболеваний, в частности первичной артериальной гипертензии, депрессивных состояний.

Цель исследования состояла в изучении влияния аргинин-вазопрессина на параметры электрической активности нейронов циркадианного осциллятора.

Материалы и методы. Эксперименты выполнены in vitro на переживающих срезах гипоталамуса крыс-самцов линии Вистар. С помощью электрофизиологической техники микроэлектродной регистрации изучали влияние аппликаций 20 нМ вазопрессина в перфузионный раствор на параметры спайковой активности нейронов супрахиазматического ядра.

Результаты. В супрахиазматическом ядре обнаружены нейроны с четырьмя различными типами спайковой активности: нерегулярным, регулярным, низким и залповым. Эти типы активности различались по частоте генерации потенциалов действия, энтропии распределения межспайковых интервалов, являющейся мерой нерегулярности генерации спайков, и обоюдной информации между сопряженными межспайковыми интервалами, отражающей степень паттернирования спайкового кода. Аппликации вазопрессина вызывали рост уровня активности у 52,3 % исследованных нейронов, сопровождавшийся снижением энтропии распределения межспайковых интервалов и ростом обоюдной информации между сопряженными межспайковыми интервалами, что свидетельствует о влиянии вазопрессина на параметры спайкового кодирования информации. Описанный тип реакций обнаружен у 88,8 % нейронов с низкой активностью, 64,3 % нейронов с нерегулярной активностью, 60,0 % нейронов с залповой активностью и 21,7 % нейронов с регулярной активностью. Лишь в 4,6 % случаев реакции на воздействие вазопрессина характеризовались снижением уровня спайковой активности.

Заключение. Представленные данные свидетельствуют о том, что вазопрессин, занимая одно из центральных мест в регуляции осмотического давления и тонуса кровеносных сосудов человека и млекопитающих, способен также оказывать влияние на биологические ритмы. Это влияние объясняется непосредственными эффектами данного пептида на уровне нейронов супрахиазматического ядра.

Ключевые слова: вазопрессин, супрахиазматическое ядро гипоталамуса, реабсорбция, имунноцитохимия, осморецепторы, биологические ритмы, спайковое кодирование информации.

Литература

1. Moore R.Y., Lenn N.J. A retinohypothalamic projection in the rat. J. Comp. Neurol. 1972; 146: 1–9.

2. Gai W.P., Geffen L.B., Blessing W.W. Galanin immunoreactive neurons in the human hypothalamus: colocalization with vasopressin-containing neurons. J. Comp. Neurol. 1990; 298: 265–280.

3. Mai J.K., Kedziora O., Teckhaus L., Sofroniew M.V. Evidence for subdivisions in the human suprachiasmatic nucleus. J. Comp. Neurol. 1991; 305: 508–525.

4. Moore R.Y. The organization of the human circadian rhythm. Prog. Brain Res. 1992; 93: 101–117.

5. Swaab D.F., Fliers E., Partiman T.S. The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res. 1985; 342: 37–44.

6. Sukhov R.R., Walker L.C., Rance N.E., Price D.L., Young W.S. Vasopressin and oxytocin gene expression in the human hypothalamus. J. Comp. Neurol. 1993; 337: 295–306.

7. Dai J.P., Swaab D.F., Buijs R.M. Distribution of vasopressin and vasoactive intestinal polypeptide (VIP) fibers in the human hypothalamus with special emphasis on suprachiasmatic nucleus efferent projections. J. Comp. Neurol. 1997; 383: 397–414.

8. Hofman M.A., Swaab D.F. Diurnal and seasonal rhythms of neuronal activity in the suprachiasmatic nucleus of humans. J. Biol. Rhythms. 1993; 8: 283–295.

9. Kalsbeek A., Buijs R.M., Van Heerikhuize J.J., Arts M., Van Der Woude T.P. Vasopressin-containing neurons of the suprachiasmatic nuclei inhibit corticosterone release. Brain Res. 1992; 580: 62–67.

10. Kalsbeek A., Van Heerikhuize J.J., Wortel J., Buijs R.M. A diurnal rhythm of stimulatory input to the hypothalamo-pituitary-adrenal system as revealed by timed intrahypothalamic administration of the vasopressin V1 antagonist. J. Neurosci. 1996; 16: 5555–5565.

11. Kalsbeek A., Van Der Vliet J., Buijs R.M. Decrease of endogenous vasopressin release necessary for expression of the circadian rise in plasma corticosterone: a reverse microdialysis study. J. Neuroendocrinol. 1996; 8: 299–307.

12. Buijs R.M., Van Eden C.G. The integration of stress by the hypothalamus, amygdale and prefrontal cortex: balance between the autonomic nervous system and the neuroendocrine system. Prog. Brain Res. 2000; 126: 117–132.

13. Kalsbeek A., Verhagen L.A., Schalij I., Foppen E., Saboureau M., Bothorel B., Buijs R.M., Pevet P. Opposite actions of hypothalamic vasopressin on circadian corticosterone rhythm in nocturnal versus diurnal species. Eur. J. Neurosci. 2008; 27: 818–827.

14. Cuesta M., Clesse D., Pevet P., Challet E. From daily behavior to hormonal and neurotransmitters rhythms: comparison between diurnal and nocturnal rat species. Horm. Behav. 2009; 55: 338–347.

15. Dardente H., Menet J.S., Challet E., Tournier B.B., Pevet P., Masson-Pe´vet M. Daily and circadian expression of neuropeptides in the suprachiasmatic nuclei of nocturnal and diurnal rodents. Brain Res. Mol. Brain Res. 2004; 124: 143–151.

16. Moore R.Y., Klein D.C. Visual pathways and the central neural control of a circadian rhythm in pineal serotonin N-acetyltransferase activity. Brain Res. 1974; 71: 17–33.

17. Moore R.Y. Neural control of the pineal gland. Behav. Brain Res. 1996; 73: 125–130.

18. Buijs R.M., Wortel J., Van Heerikhuize J.J., Feenstra M.G.P., Ter Horst G.J., Romijn H.J., Kalsbeek A. Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway. Eur. J. Neurosci. 1999; 11: 1535–1544.

19. Jasper M.S., Engeland W.C. Splanchnic neural activity modulates ultradian and circadian rhythms in adrenocortical secretion in awake rats. Neuroendocrinology. 1994; 59: 97–109.

20. Hoorneman E.M.D., Buijs R.M. Vasopressin fiber pathways in the rat brain following suprachiasmatic nucleus lesioning. Brain Res. 1982; 243: 235–241.

21. De Vries G.J., Buijs R.M., Sluiter A.A. Gonadal hormone actions on the morphology of the vasopressinergic innervation of the adult rat brain. Brain Res. 1984; 298: 141–145.

22. De La Iglesia H.O., Blaustein J.D., Bittman E.L. The suprachiasmatic area in the female hamster projects to neurons containing estrogen receptors and GnRH. Neuroreport. 1995; 6: 1715–1722.

23. Watson R.E., Langub M.C., Engle M.G., Maley B.E. Estrogen-receptive neurons in the anteroventral periventricular nucleus are synaptic targets of the suprachiasmatic nucleus and peri-suprachiasmatic region. Brain Res. 1995; 689: 254–264.

24. Sodersten P., Henning M., Melin P., Ludin S. Vasopressin alters female sexual behaviour by acting on the brain independently of alterations in blood pressure. Nature. 1983; 301: 608–610.

25. Sodersten P., De Vries G.J., Buijs R.M., Melin P. A daily rhythm in behavioral vasopressin sensitivity and brain vasopressin concentrations. Neurosci. Lett. 1985; 58: 37–41.

26. Sodersten P., Boer G.J., De Vries G.J., Buijs R.M., Melin P. Effects of vasopressin on female sexual behavior in male rat. Neurosci. Lett. 1986; 69: 188–191.

27. Palm I.F., Van Der Beek E.M., Wiegant V.M., Buijs R.M., Kalsbeek A. The stimulatory effect of vasopressin on the luteinizing hormone surge in ovariectomized, estradiol-treated rats is time-dependent. Brain Res. 2001; 901: 109–116.

28. Everett J.W., Sawyer C.H. A 24-hour periodicity in the ‘LH release apparatus’of female rats, disclosed by barbiturate sedation. Endocrinology. 1950; 47: 198–218.

29. Palm I.F., Van Der Beek E.M., Wiegant V.M., Buijs R.M., Kalsbeek A. Vasopressin induces an LH surge in ovariectomized, estradiol-treated rats with lesion of the suprachiasmatic nucleus. Neuroscience. 1999; 93: 659–666.

30. Funabashi T., Shinohara K., Mitsushima D., Kimura F. Gonadotropinreleasing hormone exhibits circadian rhythm in phase with arginine-vasopressin in co-cultures of the female rat preoptic area and suprachiasmatic nucleus. J. Neuroendocrinol. 2000; 12: 521–528.

31. Miller B.H., Olson S.L., Levine J.E., Turek F.W., Horton T.H., Takahashi J.S. Vasopressin regulation of the proestrous luteinizing hormone surge in wildtype and clock mutant mice. Biol. Reprod. 2006; 75: 778–784.

32. Van Der Beek E.M., Horvath T.L., Wiegant V.M., Van Den Hurk R., Buijs R.M. Evidence for a direct neuronal pathway from the suprachiasmatic nucleus to the gonadotropin-releasing hormone system: combined tracing and light and electron microscopic immunocytochemical studies. J. Comp. Neurol. 1997; 384: 569–579.

33. Van Der Beek E.M., Wiegant V.M., Van Der Donk H.A., Van Den Hurk R., Buijs R.M. Lesions of the suprachiasmatic nucleus indicate the presence of a direct vasoactive intestinal polypeptide-containing projection to gonadotrophin-releasing hormone neurons in the female rat. J. Neuroendocrinol. 1993; 5: 137–144.

34. Kalsbeek A., Garidou M.L., Palm I.F., Van Der Vliet J., Simonneaux V., Pevet P., Buijs R.M. Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin. Eur. J. Neurosci. 2000; 12: 3146–3154.

35. Kalsbeek A., Rikkers M., Vivien-Roels B., Pevet P. Vasopressin and vasoactive intestinal peptide infused in the paraventricular nucleus of the hypothalamus elevate plasma melatonin levels. J. Pineal. Res. 1993; 15: 46–52.

36. Roozendaal B., Van Gool W.A., Swaab D.F., Hoogendijk J.E., Mirmiran M. Changes in vasopressin cells of the rat suprachiasmatic nucleus with aging. Brain Res. 1987; 409: 259–264.

37. Cayetanot F., Bentivoglio M., Aujard F. Arginine-vasopressin and vasointestinal polypeptide rhythms in the suprachiasmatic nucleus of the mouse lemur reveal aging-related alterations of circadian pace-maker neurons in a non-human primate. Eur. J. Neurosci. 2005; 22: 902–910.

38. Liu R.Y., Zhou J.N., Hoogendijk W.J.G., Van Heerikhuize J., Kamphorst W., Unmehopa U.A., Hofman M.A., Swaab D.F. Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression. J. Neuropathol. Exp. Neurol. 2000; 59: 314–322.

39. Hofman M.A., Swaab D.F. Alterations in circadian rhythmicity of the vasopressin- producing neurons of the human suprachiasmatic nucleus (SCN) with aging. Brain Res. 1994; 651: 134–142.

40. Harper D.G., Stopa E.G., Kuo-Leblanc V., McKee A.C., Asayama K., Volicer L., Kowall N., Satlin A. Dorsomedial SCN neuronal subpopulations subserve different functions in human dementia. Brain. 2008; 131: 1609–1617.

41. Witting W., Mirmiran M., Bos N.P.A., Swaab D.F. Effect of light intensity on diurnal sleep-wake distribution in young and old rats. Brain Res. Bull. 1993; 30: 157–162.

42. Lucassen P.J., Hofman M.A., Swaab D.F. Increased light intensity prevents the age related loss of vasopressin-expressing neurons in the rat suprachiasmatic nucleus. Brain Res. 1995; 693: 261–266.

43. Riemersma-van der Lek R.F., Swaab D.F., Twisk J., Hol E.M., Hoogendijk W.J., Van Someren E.J. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008; 299: 2642–2655.

44. Goncharuk V.D., Van Heerikhuize J.J., Dai J.P., Swaab D.F., Buijs R.M. Neuropeptide changes in the suprachiasmatic nucleus in primary hypertension indicate functional impairment of the biological clock. J. Comp. Neurol. 2001; 431: 320–330.

45. Goncharuk V.D., van Heerikhuize J., Swaab D.F., Buijs R.M. Paraventricular nucleus of the human hypothalamus in primary hypertension: activation of corticotropin-releasing hormone neurons. J. Comp. Neurol. 2002; 443: 321–331.

46. Peters R.V., Zoeller R.T., Hennessey A.C., Stopa E.G., Anderson G., Albers H.E. The control of circadian rhythms and the levels of vasoactive intestinal peptide messenger RNA in the suprachiasmatic nucleus are altered in spontaneously hypertensive rats. Brain Res. 1994; 639: 217–227.

47. Avidor R., Eilam R., Malach R., Gozes I. VIP-mRNA is increased in hypertensive rats. Brain Res. 1989; 503: 304–307.

48. Scheer F.A., Van Montfrans G.A., Van Someren E.J., Mairuhu G., Buijs R.M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004; 43: 192–197.

49. Zhou J.N., Riemersma R.F., Unmehopa U.A., Hoogendijk W.J., Van Heerikhuize J.J., Hofman M.A., Swaab D.F. Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression. Arch. Gen. Psychiatry. 2001; 58: 655–662.

50. Bakker J., Brand T., Van Ophemert J., Slob A.K. Hormonal regulation of adult partner preference behavior in neonatally ATD-treated male rats. Behav. Neurosci. 1993; 107: 480–487.

51. Swaab D.F., Slob A.K., Houtsmuller E.J., Brand T., Zhou J.N. Increased number of vasopressin neurons in the suprachiasmatic nucleus (SCN) of ‘bisexual’adult male rats following perinatal treatment with the aromatase blocker ATD. Brain Res. Dev. Brain Res. 1995; 85: 273–279.

52. Ingram C.D., Ciobanu R., Coculescu I.L., Tanasescu R., Coculescu M., Mihai R. Vasopressin neurotransmission and the control of circadian rhythms in the suprachiasmatic nucleus. Prog. Brain Res. 1998; 119: 351–364.

53. Sofroniew M.V., Weindl A. Identification of parvocellular vasopressin and neurophysin neurons in the suprachiasmatic nucleus of a variety of mammals including primates. J. Comp. Neurol. 1980; 193: 659–675.

54. Moore R.Y., Speh J.C. GABA is the principal neurotransmitter of the circadian system. Neurosci. Lett. 1993; 150: 112–116.

55. Madeira M.D., Andrade J.P., Lieberman A.R., Sousa N., Almeida O.F.X., Paula-Barbosa M.M. Chronic alcohol consumption and withdrawal do not induce cell death in the suprachiasmatic nucleus, but lead to irreversible depression of peptide immunoreactivity and mRNA levels. J. Neurosci. 1997; 17: 1302–1319.

56. Kalsbeek A., Buijs R.M., Engelmann M., Wotjak C.T., Landgraf R. In vivo measurement of a diurnal variation in vasopressin release in the rat suprachiasmatic nucleus. Brain Res. 1995; 682: 75–82.

57. Kubota M., Landgraf R., Wotjak C.T. Release of vasopressin within the rat suprachiasmatic nucleus: no effect of a V1/V2 antagonist. Neuroreport. 1996; 7: 1933–1936.

58. Van den Pol A.N., Gorcs T. Synaptic relationships between neurons containing vasopressin, gastrin-releasing peptide, vasoactive intestinal polypeptide, and glutamate decarboxylase immunoreactivity in the suprachiasmatic nucleus: dual ultrastructural immunocytochemistry with gold-substituted silver peroxidase. J. Comp. Neurol. 1986; 252: 507–521.

59. Castel M., Feinstein N., Cohen S., Harari N. Vasopressinergic innervation of the mouse suprachiasmatic nucleus: an immuno-electron microscopic analysis. J. Comp. Neurol. 1990; 298: 172–187.

60. Buijs R.M., Wortel J., Hou Y.X. Colocalization of gamma-aminobutyric acid with vasopressin, vasoactive intestinal peptide, and somatostatin in the rat suprachiasmatic nucleus. J. Comp. Neurol. 1995; 358: 343–352.

61. Romijn H.J., Sluiter A.A., Pool C.W., Wortel J., Buijs R.M. Evidence from confocal fluorescence microscopy for a dense, reciprocal innervation between AVP-, somatostatin-, VIP/PHI-, GRP-, and VIP/PHI/GRP-immunoreactive neurons in the rat suprachiasmatic nucleus. Eur. J. Neurosci. 1997;
9: 2613–2623.

62. Ludwig M., Leng G. Dendritic peptide release and peptide-dependent behaviours. Nat. Rev. Neurosci. 2006; 7: 126–136.

63. Castel M., Morris J., Belenky M. Non-synaptic and dendritic exocytosis from dense-cored vesicles in the suprachiasmatic nucleus. Neuroreport. 1996; 7: 543–547.

64. Ingram C.D., Snowball R.K., Mihai R. Circadian rhythm of neuronal activity in suprachiasmatic nucleus slices from the vasopressin-deficient Brattleboro rat. Neuroscience. 1996; 75: 635–641.

65. Hamada T., Shibata S., Tsuneyoshi A., Tominaga K., Watanabe S. Effect of somatostatin on circadian rhythms of firing and 2-deoxyglucose uptake in rat suprachiasmatic slices. Am. J. Physiol. 1993; 65: 1199–1204.

66. Albers H.E., Ferris C.F., Leeman S.E., Goldman B.D. Avian pancreatic polypeptide phase shifts hamster circadian rhythms when microinjected into the suprachiasmatic region. Science. 1984; 223: 833–835.

67. Инюшкин А.Н., Петрова А.А., Ткачева М.А., Инюшкина Е.М. Влияние нейропептида Y на спайковую активность нейронов супрахиазматического ядра крыс in vitro. Российский физиологический журнал им. И.М. Сеченова. 2015; 101 (11): 1257–1269.

Download article

DOI: 10.23648/UMBJ.2018.29.11371

ROLE OF ARGININE-VAZOPRESSIN IN REGULATION OF CIRCADIAN RHYTHM NEURONS OF SUPRACHIASMATIC HYPOTHALAMUS NUCLEUS

M.A. Tkacheva, E.M. Inyushkina, S.D. Karyan, A.N. Inyushkin

Samara National Research University, Samara, Russia

e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Arginine-vasopressin is the most common neuropeptide in neurons of the suprachiasmatic nucleus of mammals, which acts as the main circadian oscillator. Vasopressinergic neurons of the suprachiasmatic nucleus undergo a daily rhythm: they grow in the daytime, but vasopressin production increases in the morning. This rhythm is important for cyclical daily regulation of hormonal hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, and for the autonomic nervous system tonus. Vasopressinergic neurons of the suprachiasmatic nucleus are involved in the pathogenesis of various diseases, namely, arterial hypertension, and depressive states.

The objective of the study was to analyze the effect of arginine-vasopressin on neuronal electrical activity in a circadian oscillator.

Materials and Methods. The experiments were conducted in vitro on dead-end sections of male Wistar rats’ hypothalamus. Electrophysiological method for microelectrode registration was used to study the effect of 20 nM vasopressin applications in the perfused solution on the parameters of the spike activity of suprachiasmatic nucleus neurons.

Results. Neurons with four different types of spike activity were found in the suprachiasmatic nucleus: irregular, regular, low and volatile. These types of activity differed in the frequency of action potentials, entropy distribution of inter-spike intervals, which is a measure of spike generation irregularity, and information between adjacent interspike intervals, reflecting the degree of spike code patterning. Vasopressin application caused an increase in neuronal activity (52.3 %). It was accompanied by a decrease in the entropy of inter-spike interval distribution and an increase in information between the adjacent inter-spike intervals. The abtained data indicate vasopressin influence on the parameters of spike information coding. The abovementioned reactions were found in 88.8% of neurons with low activity, 64.3 % of neurons with irregular activity, 60.0% of neurons with volatile activity and 21.7 % of neurons with regular activity. Only in 4.6 %, the reactions to vasopressin effects were accompanied by a decrease in the spike activity level.

Conclusion. The data obtained indicate that vasopressin, being one of the main regulators of osmotic pressure and blood vessel tonus in humans and mammals, is also able to influence biological rhythms. This influence is explained by the short-range effects of this peptide at the level of suprachiasmatic nucleus neurons.

Keywords: vasopressin, suprachiasmatic hypothalamus nucleus, reabsorption, immunocytochemistry, osmoreceptors, biological rhythms, spike information coding.

References

1. Moore R.Y., Lenn N.J. A retinohypothalamic projection in the rat. J. Comp. Neurol. 1972; 146: 1–9.

2. Gai W.P., Geffen L.B., Blessing W.W. Galanin immunoreactive neurons in the human hypothalamus: colocalization with vasopressin-containing neurons. J. Comp. Neurol. 1990; 298: 265–280.

3. Mai J.K., Kedziora O., Teckhaus L., Sofroniew M.V. Evidence for subdivisions in the human suprachiasmatic nucleus. J. Comp. Neurol. 1991; 305: 508–525.

4. Moore R.Y. The organization of the human circadian rhythm. Prog. Brain Res. 1992; 93: 101–117.

5. Swaab D.F., Fliers E., Partiman T.S. The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain. Res. 1985; 342: 37–44.