Download PDF
Pharmacopsychiatry 2023; 56(03): 101-107
DOI: 10.1055/a-1151-4947
Review

Synchronization of Fibroblasts Ex Vivo in Psychopharmacology

Frank Faltraco
1   Department of Psychiatry and Psychotherapy, University Medical Center Rostock, Rostock, Germany
,
Adriana Uzoni
1   Department of Psychiatry and Psychotherapy, University Medical Center Rostock, Rostock, Germany
,
Liliia Shevchuk
1   Department of Psychiatry and Psychotherapy, University Medical Center Rostock, Rostock, Germany
,
Johannes Thome
1   Department of Psychiatry and Psychotherapy, University Medical Center Rostock, Rostock, Germany
,
Denise Palm
1   Department of Psychiatry and Psychotherapy, University Medical Center Rostock, Rostock, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

The central oscillator for the inner clock is the suprachiasmatic nuclei of the hypothalamus. Furthermore, many peripheral oscillators are present in tissues such as skin. Human derived fibroblasts provide an advantageous model to study circadian rhythmicity as well as the influence of pharmacological drugs on circadian gene expression. Importantly, the synchronization of the circadian system of fibroblasts can be done by different methods. The review presents an overview of the current knowledge of different synchronization methods mostly used in mice or rat fibroblasts. Furthermore, the review sums up and discusses the role of norepinephrine as a possible synchronizer agent.

Key words

fibroblasts - circadian rhythm - synchronization


Publication History

Received: 28 December 2018
Received: 05 March 2020

Accepted: 01 April 2020

Article published online:
27 April 2020

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Czeisler CA, Duffy JF, Shanahan TL. et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 1999; 284: 2177-2181
    CrossrefPubMedGoogle Scholar
  • 2 Moore RY. Circadian rhythms: basic neurobiology and clinical applications. Annu Rev Med 1997; 48: 253-266
    CrossrefPubMedGoogle Scholar
  • 3 Reppert SW, Weaver DR. Coordination of circadian timing in mammals. Nature 2002; 418: 935-941
    CrossrefPubMedGoogle Scholar
  • 4 Johnson C. Testing the adaptive value of circadian systems. Methods Enzymol 2005; 393: 818-837
    CrossrefPubMedGoogle Scholar
  • 5 Noguchi T, Ikeda M, Ohmiya Y. et al. A dual-color luciferase assay system reveals circadian resetting of cultured fibroblasts by co-cultured adrenal glands. PLoS One 2012; 7: e37093
    CrossrefPubMedGoogle Scholar
  • 6 Hastings MH. Circadian biology: fibroblast clocks keep ticking. Curr Biol 2005; 15: R16-R18
    CrossrefPubMedGoogle Scholar
  • 7 Balsalobre AD, Damiola F, Schibler U. A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 1998; 93: 929-937
    CrossrefPubMedGoogle Scholar
  • 8 Balsalobre AB, Brown SA, Marcacci L. et al. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 2000; 289: 2344-2347
    CrossrefPubMedGoogle Scholar
  • 9 Manella G, Asher G. The circadian nature of mitochondrial biology. Front Endocrinol (Lausanne) 2016; 7: 162
    CrossrefPubMedGoogle Scholar
  • 10 Sardon Puig L, Valera-Alberni M, Canto C. et al. Circadian rhythms and mitochondria: connecting the dots. Front Genet 2018; 9: 452
    CrossrefPubMedGoogle Scholar
  • 11 Scrima R, Cela O, Merla G. et al. Clock-genes and mitochondrial respiratory activity: evidence of a reciprocal interplay. Biochim Biophys Acta 2016; 1857: 1344-1351
    CrossrefPubMedGoogle Scholar
  • 12 Pacelli C, Rotundo G, Lecce L. et al. Parkin mutation affects clock gene-dependent energy metabolism. Int J Mol Sci 2019; 20: 2772
    CrossrefPubMedGoogle Scholar
  • 13 Nagoshi E, Saini C, Bauer C. et al. Circadian gene expression in individual fibroblasts: cell-autonomous and self-sustained oscillators pass time to daughter cells. Cell 2004; 119: 693-705
    CrossrefPubMedGoogle Scholar
  • 14 Izumo M, Sato TR, Straume M. et al. Quantitative analyses of circadian gene expression in mammalian cell cultures. PLoS Comput Biol 2006; 2: e136
    CrossrefPubMedGoogle Scholar
  • 15 O’Neill JS, Reddy AB. The essential role of cAMP/Ca2+signalling in mammalian circadian timekeeping. Biochem Soc Trans 2012; 40: 44-50
    CrossrefPubMedGoogle Scholar
  • 16 Mendoza-Milla C, Machuca Rodriguez C, Cordova Alarcon E. et al. NF-kappaB activation but not PI3K/Akt is required for dexamethasone dependent protection against TNF-alpha cytotoxicity in L929 cells. FEBS Lett 2005; 579: 3947-3952
    CrossrefPubMedGoogle Scholar
  • 17 Nussey S, Whitehead S. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers; 2001
    Google Scholar
  • 18 Grad I, Picard D. The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol 2007; 275: 2-12
    CrossrefPubMedGoogle Scholar
  • 19 Kassel O, Herrlich P. Crosstalk between the glucocorticoid receptor and other transcription factors: molecular aspects. Mol Cell Endocrinol 2007; 275: 13-29
    CrossrefPubMedGoogle Scholar
  • 20 Bertorelli G, Bocchino V, Olivieri D. Heat shock protein interactions with the glucocorticoid receptor. Pulm Pharmacol Ther 1998; 11: 7-12
    CrossrefPubMedGoogle Scholar
  • 21 Dickmeis T, Lahiri K, Nica G. et al. Glucocorticoids play a key role in circadian cell cycle rhythms. PLoS Biol 2007; 5: e78
    CrossrefPubMedGoogle Scholar
  • 22 Ramakrishnan R, DuBois DC, Almon RR. et al. Fifth-generation model for corticosteroid pharmacodynamics: application to steady-state receptor down-regulation and enzyme induction patterns during seven-day continuous infusion of methylprednisolone in rats. J Pharmacokinet Pharmacodyn 2002; 29: 1-24
    CrossrefPubMedGoogle Scholar
  • 23 Moisan MP, Minni AM, Dominguez G. et al. Role of corticosteroid binding globulin in the fast actions of glucocorticoids on the brain. Steroids 2014; 81: 109-115
    CrossrefPubMedGoogle Scholar
  • 24 Bieler J, Cannavo R, Gustafson K. et al. Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells. Mol Syst Biol 2014; 10: 739
    CrossrefPubMedGoogle Scholar
  • 25 Fouty B, Moss T, Solodushko V. et al. Dexamethasone can stimulate G1-S phase transition in human airway fibroblasts in asthma. Eur Respir J 2006; 27: 1160-1167
    CrossrefPubMedGoogle Scholar
  • 26 Zhang Y, Giacchetti S, Parouchev A. et al. Dosing time dependent in vitro pharmacodynamics of Everolimus despite a defective circadian clock. Cell Cycle 2018; 17: 33-42
    CrossrefPubMedGoogle Scholar
  • 27 Oike H, Kobori M. Resveratrol regulates circadian clock genes in Rat-1 fibroblast cells. Biosci Biotechnol Biochem 2008; 72: 3038-3040
    CrossrefPubMedGoogle Scholar
  • 28 Park I, Lee Y, Kim HD. et al. Effect of resveratrol, a SIRT1 activator, on the interactions of the CLOCK/BMAL1 Complex. Endocrinol Metab (Seoul) 2014; 29: 379-387
    CrossrefPubMedGoogle Scholar
  • 29 Zhou B, Zhang Y, Zhang F. et al. CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1. Hepatology 2014; 59: 2196-2206
    CrossrefPubMedGoogle Scholar
  • 30 Sun L, Wang Y, Song Y. et al. Resveratrol restores the circadian rhythmic disorder of lipid metabolism induced by high-fat diet in mice. Biochem Biophys Res Commun 2015; 458: 86-91
    CrossrefPubMedGoogle Scholar
  • 31 Tan X, Li L, Wang J. et al. Resveratrol prevents acrylamide-induced mitochondrial dysfunction and inflammatory responses via targeting circadian regulator bmal1 and cry1 in hepatocytes. J Agric Food Chem 2019; 67: 8510-8519
    CrossrefPubMedGoogle Scholar
  • 32 Yao H, Sundar IK, Huang Y. et al. Disruption of sirtuin 1-mediated control of circadian molecular clock and inflammation in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2015; 53: 782-792
    CrossrefPubMedGoogle Scholar
  • 33 Lagouge M, Argmann C, Gerhart-Hines Z. et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127: 1109-1122
    CrossrefPubMedGoogle Scholar
  • 34 Liu C, Li S, Liu T. et al. Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism. Nature 2007; 447: 477-481
    CrossrefPubMedGoogle Scholar
  • 35 Li S, Chen XW, Yu L. et al. Circadian metabolic regulation through crosstalk between casein kinase 1 delta and transcriptional coactivator PGC-1alpha. Mol Endocrinol 2011; 25: 2084-2093
    CrossrefPubMedGoogle Scholar
  • 36 Li S, Lin JD. Transcriptional control of circadian metabolic rhythms in the liver. Diabetes Obes Metab 2015; 17 Suppl 1 33-38
    CrossrefPubMedGoogle Scholar
  • 37 Yagita KT, Tamanini F, van Der Horst GTJ. et al. Molecular mechanisms of the biological clock in cultured fibroblasts. Science 2001; 13: 278-281
    CrossrefPubMedGoogle Scholar
  • 38 Tamaru T, Hattori M, Honda K. et al. Synchronization of circadian Per2 rhythms and HSF1-BMAL1:CLOCK interaction in mouse fibroblasts after short-term heat shock pulse. PLoS One 2011; 6: e24521
    CrossrefPubMedGoogle Scholar
  • 39 Simonneaux V, Ribelayga C. Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev 2003; 55: 325-395
    CrossrefPubMedGoogle Scholar
  • 40 Terbeck S, Savulescu J, Chesterman LP. et al. Noradrenaline effects on social behaviour, intergroup relations, and moral decisions. Neurosci Biobehav Rev 2016; 66: 54-60
    CrossrefPubMedGoogle Scholar
  • 41 Xu FY, Gainetdinox RR, Wetsel W. et al. Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 2000; 3: 465-471
    CrossrefPubMedGoogle Scholar
  • 42 Xing B, Li YC, Gao WJ. Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex. Brain Res 2016; 1641: 217-233
    CrossrefPubMedGoogle Scholar
  • 43 Kaumann AJ, Molenaar P. Modulation of human cardiac function through 4 beta-adrenoceptor populations. Naunyn Schmiedebergs Arch Pharmacol 1997; 355: 667-681
    CrossrefPubMedGoogle Scholar
  • 44 Sarsero D, Molenaar P, Kaumann AJ. et al. Putative beta 4-adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (-)-[3H]-CGP 12177 binding. Br J Pharmacol 1999; 128: 1445-1460
    CrossrefPubMedGoogle Scholar
  • 45 Granneman JG. The putative beta 4-adrenergic receptor is a novel state of the beta1-adrenergic receptor. Am J Physiol Endocrinol Metab 2001; 280: E199-E202
    CrossrefPubMedGoogle Scholar
  • 46 Lewis CJ, Gong H, Brown MJ. et al. Overexpression of beta 1-adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for ‘putative’ beta 4-adrenoceptor pharmacology. Br J Pharmacol 2004; 141: 813-824
    CrossrefPubMedGoogle Scholar
  • 47 Wootten D, Christopoulos A, Marti-Solano M. et al. Mechanisms of signalling and biased agonism in G protein-coupled receptors. Nat Rev Mol Cell Biol 2018; 19: 635-653
    CrossrefPubMedGoogle Scholar
  • 48 Dahl EF, Wu SC, Healy CL. et al. Subcellular compartmentalization of proximal Galphaq-receptor signaling produces unique hypertrophic phenotypes in adult cardiac myocytes. J Biol Chem 2018; 293: 8734-8749
    CrossrefPubMedGoogle Scholar
  • 49 Birnbaum SG, Yuan PX, Wang M. et al. Protein kinase C overactivity impairs prefrontal cortical regulation of working memory. Science 2004; 306: 882-884
    CrossrefPubMedGoogle Scholar
  • 50 MacDonald E, Kobilka BK, Scheinin M. Gene targeting—homing in on alpha 2-adrenoceptor-subtype function. Trends Pharmacol Sci 1997; 18: 211-219
    CrossrefPubMedGoogle Scholar
  • 51 Steinkraus V, Mak JC, Pichlmeier U. et al. Autoradiographic mapping of beta-adrenoceptors in human skin. Arch Dermatol Res 1996; 288: 549-553
    CrossrefPubMedGoogle Scholar
  • 52 Gillbro JM, Marles LK, Hibberts NA. et al. Autocrine catecholamine biosynthesis and the beta-adrenoceptor signal promote pigmentation in human epidermal melanocytes. J Invest Dermatol 2004; 123: 346-353
    CrossrefPubMedGoogle Scholar
  • 53 Dwivedi Y, Pandey GN. Adenylyl cyclase-cyclic AMP signaling in mood disorders: role of the crucial phosphorylating enzyme protein kinase A. Neuropsychiatr Dis Treat 2008; 4: 161-176
    CrossrefPubMedGoogle Scholar
  • 54 Romana-Souza B, Otranto M, Almeida TF. et al. Stress-induced epinephrine levels compromise murine dermal fibroblast activity through beta-adrenoceptors. Exp Dermatol 2011; 20: 413-419
    CrossrefPubMedGoogle Scholar
  • 55 Pullar CE, Isseroff RR. The beta 2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms. J Cell Sci 2006; 119: 592-602
    CrossrefPubMedGoogle Scholar
  • 56 Shelton RC, Mainer DH, Sulser F. cAMP-dependent protein kinase activity in major depression. Am J Psychiatry 1996; 153: 1037-1042
    CrossrefPubMedGoogle Scholar
  • 57 Morioka N, Sugimoto T, Tokuhara M. et al. Noradrenaline induces clock gene Per1 mRNA expression in C6 glioma cells through β2-adrenergic receptor coupled with protein kinase A-cAMP response element binding protein (PKA-CREB) and Src-tyrosine kinase- glycogen synthase kinase-3β (Src-GSK-3β). J Pharmacological Sciences 2010; 113: 234-245
    CrossrefPubMedGoogle Scholar
  • 58 Maletic V, Eramo A, Gwin K. et al. The role of norepinephrine and its alpha-adrenergic receptors in the pathophysiology and treatment of major depressive disorder and schizophrenia: a systematic review. Front Psychiatry 2017; 8: 42
    CrossrefPubMedGoogle Scholar
  • 59 Bikle DD, Xie Z, Tu CL. Calcium regulation of keratinocyte differentiation. Expert Rev Endocrinol Metab 2012; 7: 461-472
    CrossrefPubMedGoogle Scholar
  • 60 Akiyama M, Minami Y, Kuriyama K. et al. MAP kinase-dependent induction of clock gene expression by α1-adrenergic receptor activation. FEBS Letters 2003; 542: 109-114
    CrossrefPubMedGoogle Scholar
  • 61 Durgan DJ, Hotze MA, Tomlin TM. et al. The intrinsic circadian clock within the cardiomyocyte. Am J Physiol Heart Circ Physiol 2005; 289: H1530-H1541
    CrossrefPubMedGoogle Scholar
  • 62 Terazono HM, Mutoh T, Yamaguchi S. et. al. Adrenergic regulation of clock gene expression in mouse liver. Proc Natl Acad Sci USA 2003; 100: 6795-6800
    CrossrefPubMedGoogle Scholar
  • 63 Li Y, Cassone VM. Clock-controlled regulation of the acute effects of norepinephrine on chick pineal melatonin rhythms. J Biol Rhythms 2015; 30: 519-532
    CrossrefPubMedGoogle Scholar
  • 64 Chalmers JA, Martino TA, Tata N. et al. Vascular circadian rhythms in a mouse vascular smooth muscle cell line (Movas-1). Am J Physiol Regul Integr Comp Physiol 2008; 295: R1529-R1538
    CrossrefPubMedGoogle Scholar
  • 65 Andrade-Silva J, Cipolla-Neto J, Peliciari-Garcia RA. The in vitro maintenance of clock genes expression within the rat pineal gland under standard and norepinephrine-synchronized stimulation. Neurosci Res 2014; 81–82: 1-10
    CrossrefPubMedGoogle Scholar
  • 66 Johansson AS, Owe-Larsson B, Hetta J. et al. Altered circadian clock gene expression in patients with schizophrenia. Schizophr Res 2016; 174: 17-23
    CrossrefPubMedGoogle Scholar
  • 67 Cronin P, McCarthy MJ, Lim ASP. et al. Circadian alterations during early stages of Alzheimer’s disease are associated with aberrant cycles of DNA methylation in BMAL1. Alzheimers Dement 2017; 13: 689-700
    CrossrefPubMedGoogle Scholar
  • 68 McCarthy MJ, Fernandes M, Kranzler HR. et al. Circadian clock period inversely correlates with illness severity in cells from patients with alcohol use disorders. Alcohol Clin Exp Res 2013; 37: 1304-1310
    CrossrefPubMedGoogle Scholar
  • 69 Lippert J, Halfter H, Heidbreder A. et al. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia. PLoS One 2014; 9: e85255
    CrossrefPubMedGoogle Scholar
  • 70 Mansour HA, Wood J, Chowdari KV. et al. Associations between period 3 gene polymorphisms and sleep-/chronotype-related variables in patients with late-life insomnia. Chronobiol Int 2017; 34: 624-631
    CrossrefPubMedGoogle Scholar
  • 71 Yang S, Van Dongen HP, Wang K. et al. Assessment of circadian function in fibroblasts of patients with bipolar disorder. Mol Psychiatry 2009; 14: 143-155
    CrossrefPubMedGoogle Scholar
  • 72 McCarthy MJ, Wei H, Marnoy Z. et al. Genetic and clinical factors predict lithium’s effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Transl Psychiatry 2013; 3: e318
    CrossrefPubMedGoogle Scholar
  • 73 Coogan AN, Schenk M, Palm D. et al. Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms. Neuropsychopharmacology 2019; 44: 1198-1206
    CrossrefPubMedGoogle Scholar
  • 74 Marien MR, Colpaert FC, Rosenquist AC. Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res Brain Res Rev 2004; 45: 38-78
    CrossrefPubMedGoogle Scholar
  • 75 Biederman J, Spencer T. Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry 1999; 46: 1234-1242
    CrossrefPubMedGoogle Scholar
  • 76 Beane M, Marrocco RT. Norepinephrine and acetylcholine mediation of the components of reflexive attention: implications for attention deficit disorders. Prog Neurobiol 2004; 74: 167-181
    CrossrefPubMedGoogle Scholar
  • 77 Kim C-H, Hahn MK, Joung Y. et al. A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention deficit hyperactivity disorder. Proc Natl Acad Sci USA 2006; 103: 19164-19169
    CrossrefPubMedGoogle Scholar
  • 78 Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 2005; 57: 1377-1384
    CrossrefPubMedGoogle Scholar
  • 79 Comings DE, Gonzalez NS, Cheng Li SC. et al. A “line item” approach to the identification of genes involved in polygenic behavioral disorders: the adrenergic alpha2A (ADRA2A) gene. Am J Med Genet B Neuropsychiatr Genet 2003; 118B: 110-114
    CrossrefPubMedGoogle Scholar
  • 80 Pitman RK, Delahanty DL. Conceptually driven pharmacologic approaches to acute trauma. CNS Spectr 2005; 10: 99-106
    CrossrefPubMedGoogle Scholar
  • 81 Bymaster FPK, Katner J, Nelson DL. et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat. Neuropsychopharmacology 2002; 27: 699-711
    CrossrefPubMedGoogle Scholar
  • 82 Swanson CJ, Perry KW, Koch-Krueger S. et al. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology 2006; 50: 755-760
    CrossrefPubMedGoogle Scholar
  • 83 Michelson DF, Faries D, Wernicke J. et al. Atomoxetien in the treatment of children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 2001; 108: e83
    CrossrefPubMedGoogle Scholar
  • 84 Spencer T, Biederman J, Heiligenstein J. et al. An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 2001; 11: 251-265
    CrossrefPubMedGoogle Scholar
  • 85 Ross JA, McGonigle P, Van Bockstaele EJ. Locus coeruleus, norepinephrine and abeta peptides in Alzheimer’s disease. Neurobiol Stress 2015; 2: 73-84
    CrossrefPubMedGoogle Scholar
  • 86 Reilly DF, Curtis AM, Cheng Y. et al. Peripheral circadian clock rhythmicity is retained in the absence of adrenergic signaling. Arterioscler Thromb Vasc Biol 2008; 28: 121-126
    CrossrefPubMedGoogle Scholar