Abstract
Somatostatin is synthesized in the suprachiasmatic nucleus (SCN), a circadian pacemaker in mammals. To explore the functional significance of somatostatin in the circadian system, we examined rhythms of rat locomotor activity and electrical firing rate of SCN neurons in the brain slice after temporal depletion of somatostatin levels in the SCN. Intraperitoneal administration of cysteamine (200 mg/kg), a somatostatin depletor, significantly reduced somatostatin level in the in vivo SCN 5 min after injection and kept low level as long as 3 to 4 days. This administration, on the other hand, induced significant phase advances of about 51 min in the subsequent free-running rhythm of locomotor activity of the rat. A marked phase advance in the circadian rhythm of firing rate in the SCN was also observed after administration of cysteamine in coronal hypothalamic slices. These persistent phase shifts after administration of a somatostatin depletor may suggest that the change of somatostatin level in the SCN have a feedback influence on the circadian pacemaker.
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Abbreviations
- SCN :
-
suprachiasmatic nucleus
- AVP :
-
arginine-vasopressin
- VIP :
-
vasoactive intestinal polypeptide
- CT :
-
circadian time
- ZT :
-
zeitgeber time
- i.p. :
-
intraperitoneally
- 12L:12D :
-
12 h light and 12 h dark
- ANOVA :
-
analysis of variance
References
Albers HE, Ferris CF (1984) Neuropeptide Y: role in light-dark entrainment of hamster circadian rhythms. Neurosci Lett 50: 163–168
Albers HE, Liou S-Y, Stopa EG, Zoeller RT (1991) Interaction of colocalized neuropeptides: functional significance in the circadian timing system. J Neurosci 11: 846–851
Card JP, Brecha N, Karten HJ, Moore RY (1981) Immunocytochemical localization of vasoactive intestinal polypeptide-containing cells and processes in the suprachiasmatic nucleus of the rat: light and electron microscopic analysis. J Neurosci 1: 1289–1303
Chan-Palay V, Záborszky L, Köhler C, Goldstein M, Palay SL (1984) Distribution of tyrosine-hydroxylase-immunoreactive neurons in the hypothalamus of rats. J Comp Neurol 227: 467–496
Daikoku S, Hisano S, Kagotani Y (1992a) Neuronal associations in the rat suprachiasmatic nucleus demonstrated by immunoelectron microscopy. J Comp Neurol 325: 559–571
Daikoku S, Yokote R, Aizawa T, Kawano H (1992b) Light stimulation of the hypothalamic neuroendocrine system. Arch Histol Cytol 55: 67–76
Fukuhara C, Shinohara K, Tominaga K, Otori Y, Inouye S-IT (1993) Endogenous circadian rhythmicity of somatostatin like-immunoreactivity in the rat suprachiasmatic nucleus. Brain Res 606: 28–35
Gillette MU (1991) SCN electrophysiology in vitro: rhythmic activity and endogenous clock properties. In: Klein DC, Moore RY, Reppert SM (eds) Suprachiasmatic nucleus. The mind's clock. Oxford Univ Press, New York, pp 125–143
Hamada T, Shibata S, Tsuneyoshi A, Tominaga K, Watanabe S (1993) Effect of somatostatin on the circadian rhythms of firing and 2-deoxyglucose uptake in the rat suprachiasmatic slices. Am J Physiol 265: R1199-R1204
Haroutunian V, Mantin R, Campbell GA, Tsuboyama GK, Davis KL (1987) Cysteamine-induced depletion of central somatostatin-like immunoreactivity: effects on behavior, learning, memory and brain neurochemistry. Brain Res 403: 234–242
Harrington ME, Nance DM, Rusak B (1987) Double-labeling of neuropeptide Y-immunoreactive neurons which project from the geniculate to the suprachiasmatic nuclei. Brain Res 410: 275–282
Ibata Y, Takahashi Y, Okamura H, Kawakami F, Terubayashi H, Kubo T, Yanaihara N (1989) Vasoactive intestinal peptide (VIP)-like immunoreactive neurons located in the rat suprachiasmatic nucleus receive a direct retinal projection. Neurosci Lett 97: 1–5
Inouye S-IT, Kawamura H (1979) Persistence of circadian rhythmicity in a hypothalamic ‘island’ containing the suprachiasmatic nucleus. Proc Natl Acad Sci USA 76: 5962–5966
Klein DC, Moore RY, Reppert SM (eds) (1991) Suprachiasmatic nucleus. The mind's clock. Oxford Univ Press, New York
Meijer JH, Rietveld WJ (1989) Neurophysiology of the suprachiasmatic circadian pacemaker in rodents. Physiol Rev 69: 671–707
Millard WJ, Sager SM, Landis DM, Martin JB (1982) Cysteamine: A potent and specific depletor of pituitary prolactin. Science 217: 452–454
Palkovits M, Brownstein MJ, Eiden LE, Beinfeld MC, Russell J, Arimura A, Szabo S (1982) Selective depletion of somatostatin in rat brain by cysteamine. Brain Res 240: 178–180
Pickard GE (1985) Bifurcating axons of retinal ganglion cells terminate in the hypothalamic suprachiasmatic nucleus and the intergeniculate leaflet of the thalamus. Neurosci Lett 55: 211–217
Prosser RA, Gillette MU (1989) The mammalian circadian clock in the suprachiasmatic nuclei is reset in vitro by cAMP. J Neurosci 9: 1073–1081
Reeth OV, Hinch D, Tecco JM, Turek FW (1991) The effects of short periods of immobilization on the hamster circadian clock. Brain Res 545: 208–214
Rusak B, Boulos Z (1981) Pathways for photic entrainment of mammalian circadian rhythms. Photochem Photobiol 34: 267–273
Rusak B, Zucker I (1979) Neural regulation of circadian rhythms. Physiol Rev 59: 449–526
Sagar SM, Landry D, Millard WJ, Badger TM, Arnold MA, Martin JB (1982) Depletion of somatostatin-like immunoreactivity in the rat central nervous system by cysteamine. J Neurosci 2: 225–231
Shibata S, Tsuneyoshi A, Hamada T, Tominaga K, Watanabe S (1992) Phase resetting effect of 8-OH-DPAT, a serotonin 1A receptor agonist, on the circadian rhythm of firing rate in the rat suprachiasmatic nuclei in vitro. Brain Res 582: 353–356
Shinohara K, Isobe Y, Takeuchi J, Inouye S-IT (1991) Circadian rhythms of somatostatin-immunoreactivity in the suprachiasmatic nucleus of the rat. Neurosci Lett 129: 59–62
Shinohara K, Tominaga K, Isobe Y, Inouye S-IT (1993) Photic regulation of peptides located in the ventrolateral subdivision of the suprachiasmatic nucleus of the rat: daily variations of vasoactive intestinal polypeptide, gastrin releasing peptide and neuropeptide Y. J Neurosci 13: 793–800
Sofroniew MV, Weindl A (1982) Neuroanatomical organization of connections of the suprachiasmatic nucleus. In: Aschoff J, Daan S, Groos GA (eds) Vertebrate circadian systems. Springer, Berlin, pp 75–86
Szabo S, Reichlin S (1981) Somatostatin in rat tissues is depleted by cysteamine administration. Endocrinology 109: 2255–2257
Szabo S, Horner HC, Maull H, Schnoor J, Chiueh CC, Palkovits M (1987) Biochemical changes in tissue catecholamines and serotonin in duodenal ulceration caused by cysteamine or propionitrile in the rat. J Pharmacol Exp Ther 240: 871–878
Tominaga K, Shinohara K, Otori Y, Fukuhara C, Inouye S-IT (1992) Circadian rhythms of vasopressin content in the suprachiasmatic nucleus of the rat. NeuroReport 3: 809–812
van den Pol AN (1980) The hypothalamic suprachiasmatic nucleus of rat: intrinsic anatomy. J Comp Neurol 191: 661–702
van den Pol AN, Tsujimoto KL (1985) Neurotransmitters of the hypothalamic suprachiasmatic nucleus: immunocytochemical analysis of 25 neuronal antigens. Neuroscience 15: 1049–1086
Yamada N, Shimoda K, Takahashi S, Takahashi K (1986) Change in period of freerunning rhythms determined by two different tools in blinded rats. Physiol Behav 36: 357–362
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Fukuhara, C., Inouye, S.I.T., Aoki, K. et al. Phase advances of circadian rhythms in somatostatin depleted rats: effects of cysteamine on rhythms of locomotor activity and electrical discharge of the suprachiasmatic nucleus. J Comp Physiol A 175, 677–685 (1994). https://doi.org/10.1007/BF00191840
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DOI: https://doi.org/10.1007/BF00191840