Norepinephrine influences the circadian clock in human dermal fibroblasts from study participants with a diagnosis of attention-deficit hyperactivity disorder.
Attention-deficit hyperactivity disorder
Circadian rhythm
Human dermal fibroblasts
Norepinephrine
Journal
Journal of neural transmission (Vienna, Austria : 1996)
ISSN: 1435-1463
Titre abrégé: J Neural Transm (Vienna)
Pays: Austria
ID NLM: 9702341
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
12
01
2021
accepted:
27
06
2021
pubmed:
19
7
2021
medline:
16
10
2021
entrez:
18
7
2021
Statut:
ppublish
Résumé
Attention-deficit hyperactivity disorder (ADHD) is characterized by changes to the circadian process. Many medications used to treat the condition, influence norepinephrine levels. Several studies have, in addition, reported that norepinephrine itself has an effect on circadian function. The aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after norepinephrine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with an ADHD diagnosis. Circadian preference was evaluated with German Morningness-Eveningness Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different norepinephrine concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. The exposure of 1 µM norepinephrine to confluent cultures of human dermal fibroblasts from participants with a diagnosis of ADHD, was shown to dampen Per1 rhythmicity. The expression of Bmal1, Per1 and Per3 in control subjects was also influenced by incubation with 1 µM norepinephrine. Cultures from the ADHD group revealed no statistically significant overall differences in circadian gene expression, between cultures with and without norepinephrine incubation. Per3 expression showed a significant ZT × group interaction via mixed ANOVA. Per3 expression at ZT4 was significant higher in the group of control samples incubated with 1 µM norepinephrine, compared to the control group without norepinephrine. This effect was also shown in the control samples incubated with 1 µM norepinephrine and cultures from subjects with ADHD without norepinephrine incubation. Per3 expression differed between the healthy control group and the ADHD group without norepinephrine incubation at ZT28. The results of the present study illustrate that norepinephrine impacts on circadian function. In both groups, control group and cultures taken from subjects with ADHD, the expression of the periodic genes (Per1-3) was significantly influenced by incubation with norepinephrine.
Identifiants
pubmed: 34275002
doi: 10.1007/s00702-021-02376-2
pii: 10.1007/s00702-021-02376-2
pmc: PMC8295072
doi:
Substances chimiques
Norepinephrine
X4W3ENH1CV
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1147-1157Subventions
Organisme : 2020 FORUN
ID : 889024
Organisme : 2020 CoCA ADHD Comorbidity
ID : 667302
Informations de copyright
© 2021. The Author(s).
Références
Andrade-Silva J, Cipolla-Neto J, Peliciari-Garcia RA (2014) The in vitro maintenance of clock genes expression within the rat pineal gland under standard and norepinephrine-synchronized stimulation. Neurosci Res 81–82:1–10. https://doi.org/10.1016/j.neures.2014.03.005
doi: 10.1016/j.neures.2014.03.005
pubmed: 24681283
Baird AL, Coogan AN, Siddiqui A, Donev RM, Thome J (2012) Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels. Mol Psychiatry 17:988–995. https://doi.org/10.1038/mp.2011.149
doi: 10.1038/mp.2011.149
pubmed: 22105622
Beane M, Marrocco RT (2004) Norepinephrine and acetylcholine mediation of the components of reflexive attention: implications for attention deficit disorders. Prog Neurobiol 74:167–181. https://doi.org/10.1016/j.pneurobio.2004.09.001
doi: 10.1016/j.pneurobio.2004.09.001
pubmed: 15556286
Biederman J, Spencer T (1999) Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry 46:1234–1242
doi: 10.1016/S0006-3223(99)00192-4
pubmed: 10560028
Burioka N et al (2008) Clock gene dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J 32:105–112. https://doi.org/10.1183/09031936.00138207
doi: 10.1183/09031936.00138207
pubmed: 18321934
Coogan AN, McGowan NM (2017) A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder. Atten Deficit Hyperact Disord 9:129–147. https://doi.org/10.1007/s12402-016-0214-5
doi: 10.1007/s12402-016-0214-5
Coogan AN, Baird AL, Popa-Wagner A, Thome J (2016) Circadian rhythms and attention deficit hyperactivity disorder: the what, the when and the why. Prog Neuropsychopharmacol Biol Psychiatry 67:74–81. https://doi.org/10.1016/j.pnpbp.2016.01.006
doi: 10.1016/j.pnpbp.2016.01.006
pubmed: 26776072
Coogan AN et al (2019) Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms. Neuropsychopharmacology 44:1198–1206. https://doi.org/10.1038/s41386-019-0327-6
doi: 10.1038/s41386-019-0327-6
pubmed: 30758328
pmcid: 6785110
Cronin P et al (2017) Circadian alterations during early stages of Alzheimer’s disease are associated with aberrant cycles of DNA methylation in BMAL1. Alzheimers Dement 13:689–700. https://doi.org/10.1016/j.jalz.2016.10.003
doi: 10.1016/j.jalz.2016.10.003
pubmed: 27883893
Culnan E, Kloss JD, Grandner M (2013) A prospective study of weight gain associated with chronotype among college freshmen. Chronobiol Int 30:682–690. https://doi.org/10.3109/07420528.2013.782311
doi: 10.3109/07420528.2013.782311
pubmed: 23688114
pmcid: 3759532
Czeisler CA et al (1999) Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 284:2177–2181
doi: 10.1126/science.284.5423.2177
pubmed: 10381883
Dankel SN et al (2014) Weight cycling promotes fat gain and altered clock gene expression in adipose tissue in C57BL/6J mice. Am J Physiol Endocrinol Metab 306:E210–224. https://doi.org/10.1152/ajpendo.00188.2013
doi: 10.1152/ajpendo.00188.2013
pubmed: 24302006
Dijk DJ, Archer SN (2010) PERIOD3, circadian phenotypes, and sleep homeostasis Sleep Med Rev 14:151–160. https://doi.org/10.1016/j.smrv.2009.07.002
Durgan DJ et al (2005) The intrinsic circadian clock within the cardiomyocyte. Am J Physiol Heart Circ Physiol 289:H1530–1541. https://doi.org/10.1152/ajpheart.00406.2005
doi: 10.1152/ajpheart.00406.2005
pubmed: 15937094
Faltraco F, Uzoni A, Shevchuk L, Thome J, Palm D (2020) Synchronization of fibroblasts ex vivo in psychopharmacology. Pharmacopsychiatry. https://doi.org/10.1055/a-1151-4947
doi: 10.1055/a-1151-4947
pubmed: 32340062
Faltraco F, Palm D, Uzoni A, Simon F, Tucha O, Thome J (2021a) Atomoxetine and circadian gene expression in human dermal fibroblasts from participants with a diagnosis of attention-deficit hyperactivity disorder. J Neural Transm. https://doi.org/10.1007/s00702-021-02373-5 (Accepted)
doi: 10.1007/s00702-021-02373-5
pubmed: 34275002
Faltraco F, Palm D, Uzoni A, Borchert L, Simon F, Tucha O, Thome J (2021b) Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients. J Neural Transm. https://doi.org/10.1007/s00702-021-02374-4 (Accepted)
doi: 10.1007/s00702-021-02374-4
pubmed: 34275002
Faltraco F, Palm D, Coogan A, Uzoni A, Duwe I, Simon F, Tucha O, Thome J (2021c) Remdesivir shifts circadian rhythmicity to eveningness; similar to the most prevalent chronotype in ADHD. J Neural Transm. https://doi.org/10.1007/s00702-021-02375-3 (Accepted)
doi: 10.1007/s00702-021-02375-3
pubmed: 34275002
Fletcher EC (2003) Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea. Sleep 26:15–19. https://doi.org/10.1093/sleep/26.1.15
doi: 10.1093/sleep/26.1.15
pubmed: 12627727
Gillbro JM, Marles LK, Hibberts NA, Schallreuter KU (2004) Autocrine catecholamine biosynthesis and the beta-adrenoceptor signal promote pigmentation in human epidermal melanocytes. J Investig Dermatol 123:346–353. https://doi.org/10.1111/j.0022-202X.2004.23210.x
doi: 10.1111/j.0022-202X.2004.23210.x
pubmed: 15245435
Johansson AS, Owe-Larsson B, Hetta J, Lundkvist GB (2016) Altered circadian clock gene expression in patients with schizophrenia. Schizophr Res 174:17–23. https://doi.org/10.1016/j.schres.2016.04.029
doi: 10.1016/j.schres.2016.04.029
pubmed: 27132483
Korman M, Palm D, Uzoni A, Faltraco F, Tucha O, Thome J, Coogan AN (2018) ADHD 24/7: circadian clock genes, chronotherapy and sleep/wake cycle insufficiencies in ADHD. World J Biol Psychiatry. https://doi.org/10.1080/15622975.2018.1523565
doi: 10.1080/15622975.2018.1523565
pubmed: 30234417
Li Y, Cassone VM (2015) Clock-controlled regulation of the acute effects of norepinephrine on chick pineal melatonin rhythms. J Biol Rhythms 30:519–532. https://doi.org/10.1177/0748730415607060
doi: 10.1177/0748730415607060
pubmed: 26446873
Lippert J et al (2014) Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia. PLoS ONE 9:e85255. https://doi.org/10.1371/journal.pone.0085255
doi: 10.1371/journal.pone.0085255
pubmed: 24454829
pmcid: 3891749
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
doi: 10.1006/meth.2001.1262
pubmed: 11846609
Lucassen EA et al (2013) Evening chronotype is associated with changes in eating behavior, more sleep apnea, and increased stress hormones in short sleeping obese individuals. PLoS ONE 8:e56519. https://doi.org/10.1371/journal.pone.0056519
doi: 10.1371/journal.pone.0056519
pubmed: 23483886
pmcid: 3590198
MacDonald E, Kobilka BK, Scheinin M (1997) Gene targeting–homing in on alpha 2-adrenoceptor-subtype function. Trends Pharmacol Sci 18:211–219
doi: 10.1016/S0165-6147(97)90625-8
pubmed: 9227000
Mane VP, Heuer MA, Hillyer P, Navarro MB, Rabin RL (2008) Systematic method for determining an ideal housekeeping gene for real-time PCR analysis. J Biomol Tech 19:342–347
pubmed: 19183798
pmcid: 2628067
Mansour HA et al (2017) Associations between period 3 gene polymorphisms and sleep- /chronotype-related variables in patients with late-life insomnia. Chronobiol Int 34:624–631. https://doi.org/10.1080/07420528.2017.1287083
doi: 10.1080/07420528.2017.1287083
pubmed: 28276850
pmcid: 5403599
Marien MR, Colpaert FC, Rosenquist AC (2004) Noradrenergic mechanisms in neurodegenerative diseases: a theory. Brain Res Brain Res Rev 45:38–78. https://doi.org/10.1016/j.brainresrev.2004.02.002
doi: 10.1016/j.brainresrev.2004.02.002
pubmed: 15063099
McCarthy MJ, Fernandes M, Kranzler HR, Covault JM, Welsh DK (2013a) Circadian clock period inversely correlates with illness severity in cells from patients with alcohol use disorders. Alcohol Clin Exp Res 37:1304–1310. https://doi.org/10.1111/acer.12106
doi: 10.1111/acer.12106
pubmed: 23550834
pmcid: 3706548
McCarthy MJ, Wei H, Marnoy Z, Darvish RM, McPhie DL, Cohen BM, Welsh DK (2013b) Genetic and clinical factors predict lithium’s effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Transl Psychiatry 3:e318. https://doi.org/10.1038/tp.2013.90
doi: 10.1038/tp.2013.90
pubmed: 24150227
pmcid: 3818008
McGowan NM, Uzoni A, Faltraco F, Thome J, Coogan AN (2020) The impact of social jetlag and chronotype on attention, inhibition and decision making in healthy adults. J Sleep Res. https://doi.org/10.1111/jsr.12974
doi: 10.1111/jsr.12974
pubmed: 31943451
Menet JS, Rodriguez J, Abruzzi KC, Rosbash M (2012) Nascent-Seq reveals novel features of mouse circadian transcriptional regulation. Elife 1:e00011. https://doi.org/10.7554/eLife.00011
doi: 10.7554/eLife.00011
pubmed: 23150795
pmcid: 3492862
Moore RY (1997) Circadian rhythms: basic neurobiology and clinical applications. Annu Rev Med 48:253–266. https://doi.org/10.1146/annurev.med.48.1.253
doi: 10.1146/annurev.med.48.1.253
pubmed: 9046960
Morioka N, Sugimoto T, Tokuhara M, Dohi T, Nakata Y (2010) 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 Pharmacol Sci 113:234–245. https://doi.org/10.1254/jphs.10031FP
doi: 10.1254/jphs.10031FP
pubmed: 20595783
Pegoraro M, Picot E, Hansen CN, Kyriacou CP, Rosato E, Tauber E (2015) Gene expression associated with early and late chronotypes in Drosophila melanogaster. Front Neurol 6:100. https://doi.org/10.3389/fneur.2015.00100
doi: 10.3389/fneur.2015.00100
pubmed: 26097463
pmcid: 4457141
Phillips C, Fahimi A, Das D, Mojabi FS, Ponnusamy R, Salehi A (2016) Noradrenergic system in down syndrome and Alzheimer’s disease a target for therapy. Curr Alzheimer Res 13:68–83. https://doi.org/10.2174/1567205012666150921095924
doi: 10.2174/1567205012666150921095924
pubmed: 26391048
Reppert SW, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941
doi: 10.1038/nature00965
pubmed: 12198538
Sharma A, Couture J (2014) A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). Ann Pharmacother 48:209–225. https://doi.org/10.1177/1060028013510699
doi: 10.1177/1060028013510699
pubmed: 24259638
Simonneaux V, Ribelayga C (2003) 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 55:325–395. https://doi.org/10.1124/pr.55.2.2
doi: 10.1124/pr.55.2.2
pubmed: 12773631
Steinkraus V, Mak JC, Pichlmeier U, Mensing H, Ring J, Barnes PJ (1996) Autoradiographic mapping of beta-adrenoceptors in human skin. Arch Dermatol Res 288:549–553
doi: 10.1007/BF02505253
pubmed: 8874751
Strober W (2015) Trypan blue exclusion test of cell viability. Curr Protoc Immunol 111:A3 B 1-A3 B 3. https://doi.org/10.1002/0471142735.ima03bs111
doi: 10.1002/0471142735.ima03bs111
pubmed: 26529666
Takahashi M et al (2018) Chronotype and social jetlag influence human circadian clock gene expression. Sci Rep 8:10152. https://doi.org/10.1038/s41598-018-28616-2
doi: 10.1038/s41598-018-28616-2
pubmed: 29976939
pmcid: 6033857
Takashima A (1998) Establishment of fibroblast cultures. Curr Protoc Cell Biol Chapter 2:Unit 2.1
Terazono H, Mutoh T, Yamaguchi S, Kobayashi M, Akiyama M, Udo R, Ohdo S, Okamura H, Shibata S (2003) Adrenergic regulation of clock gene expression in mouse liver. Proc Natl Acad Sci USA 100:6795
doi: 10.1073/pnas.0936797100
pubmed: 12754374
pmcid: 164526
Terbeck S, Savulescu J, Chesterman LP, Cowen PJ (2016) Noradrenaline effects on social behaviour, intergroup relations, and moral decisions. Neurosci Biobehav Rev 66:54–60. https://doi.org/10.1016/j.neubiorev.2016.03.031
doi: 10.1016/j.neubiorev.2016.03.031
pubmed: 27126289
pmcid: 4899514
Thaben PF, Westermark PO (2016) Differential rhythmicity: detecting altered rhythmicity in biological data. Bioinformatics 32:2800–2808. https://doi.org/10.1093/bioinformatics/btw309
doi: 10.1093/bioinformatics/btw309
pubmed: 27207944
Xing B, Li YC, Gao WJ (2016) Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex. Brain Res 1641:217–233. https://doi.org/10.1016/j.brainres.2016.01.005
doi: 10.1016/j.brainres.2016.01.005
pubmed: 26790349
pmcid: 4879059
Xu FYSH, Liu AC, Takahashi JS, Kay SA (2000) Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 3:465–471
doi: 10.1038/74839
pubmed: 10769386
Yang S, Van Dongen HP, Wang K, Berrettini W, Bucan M (2009) Assessment of circadian function in fibroblasts of patients with bipolar disorder. Mol Psychiatry 14:143–155. https://doi.org/10.1038/mp.2008.10
doi: 10.1038/mp.2008.10
pubmed: 18301395