Outside the Brain: an Inside View on Transgenic Animal and Stem Cell-based Models to Examine Neuronal Serotonin-dependent Regulation of HPA Axis-controlled Events During Development and Adult Stages

Overview

Journal Stem Cell Investig

Publisher AME Publishing Company

Date 2017 Jan 13

PMID 28078274

Authors

Jonas Waider

Janina Ziegler

Thorsten Lau

Affiliations

Soon will be listed here.

Abstract

Recently, Trista North and colleagues showed that neuronal synthesis of serotonin is an essential key process for embryonic hematopoietic stem (HPS) cell production in zebrafish. Using their experimental design, they were able to show that neuronal serotonin activates the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid receptor activity which in turn induces HPS cell formation. In our perspective, we give a short overview on established experimental approaches for serotonergic neurotransmission and and their potential to address putative contributions of serotonergic neurotransmission to physiological processes beyond the central nervous systems (CNS). We briefly introduce common features of brain serotonin-depleted, tryptophan hydroxylase-2 knockout mice, which can be applied to investigate the contribution of brain-derived serotonin to developmental and adult physiological processes outside the CNS. These models allow to analyzing gender-specific, HPA axis-dependent processes in female and male knockout mice during developmental and adult stages. We also highlight the application of human and mouse stem cell-derived serotonergic neurons as an independent research model as well as complementary experimental approach to transgenic animal models. In case of human serotonergic neurotransmission, human -generated neurons present a very promising and highly valuable experimental approach to address characteristics of human neuronal serotonin signaling on a molecular and cellular level. The combination of transgenic animal models and newly established stem cell technologies will provide powerful research platforms, which will help to answer yet unsolved mysteries of serotonergic neurotransmission.

References

Mouillet-Richard S, Mutel V, Loric S, Tournois C, Launay J, Kellermann O . Regulation by neurotransmitter receptors of serotonergic or catecholaminergic neuronal cell differentiation. J Biol Chem. 2000; 275(13):9186-92. DOI: 10.1074/jbc.275.13.9186. View

Chaouloff F . Serotonin, stress and corticoids. J Psychopharmacol. 2000; 14(2):139-51. DOI: 10.1177/026988110001400203. View

Sonino N, Fava G . Psychiatric disorders associated with Cushing's syndrome. Epidemiology, pathophysiology and treatment. CNS Drugs. 2001; 15(5):361-73. DOI: 10.2165/00023210-200115050-00003. View

Lai M, McCormick J, Chapman K, Kelly P, Seckl J, Yau J . Differential regulation of corticosteroid receptors by monoamine neurotransmitters and antidepressant drugs in primary hippocampal culture. Neuroscience. 2003; 118(4):975-84. DOI: 10.1016/s0306-4522(03)00038-1. View

Fairchild G, Leitch M, Ingram C . Acute and chronic effects of corticosterone on 5-HT1A receptor-mediated autoinhibition in the rat dorsal raphe nucleus. Neuropharmacology. 2003; 45(7):925-34. DOI: 10.1016/s0028-3908(03)00269-7. View

Hornung J . The human raphe nuclei and the serotonergic system. J Chem Neuroanat. 2004; 26(4):331-43. DOI: 10.1016/j.jchemneu.2003.10.002. View

Touma C, Palme R, Sachser N . Analyzing corticosterone metabolites in fecal samples of mice: a noninvasive technique to monitor stress hormones. Horm Behav. 2004; 45(1):10-22. DOI: 10.1016/j.yhbeh.2003.07.002. View

Mikkelsen J, Hay-Schmidt A, Kiss A . Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis: interaction between 5-HT1A and 5-HT2A receptors. Ann N Y Acad Sci. 2004; 1018:65-70. DOI: 10.1196/annals.1296.007. View

Slotkin T, Kreider M, Tate C, Seidler F . Critical prenatal and postnatal periods for persistent effects of dexamethasone on serotonergic and dopaminergic systems. Neuropsychopharmacology. 2005; 31(5):904-11. DOI: 10.1038/sj.npp.1300892. View

10.

Leonard B . The HPA and immune axes in stress: the involvement of the serotonergic system. Eur Psychiatry. 2006; 20 Suppl 3:S302-6. DOI: 10.1016/s0924-9338(05)80180-4. View

11.

Jacobs B, Azmitia E . Structure and function of the brain serotonin system. Physiol Rev. 1992; 72(1):165-229. DOI: 10.1152/physrev.1992.72.1.165. View

12.

Heisler L, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L . Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation. J Neurosci. 2007; 27(26):6956-64. PMC: 6672238. DOI: 10.1523/JNEUROSCI.2584-06.2007. View

13.

Flanagan R, Dunk L . Haematological toxicity of drugs used in psychiatry. Hum Psychopharmacol. 2007; 23 Suppl 1:27-41. DOI: 10.1002/hup.917. View

14.

Lanfumey L, Mongeau R, Cohen-Salmon C, Hamon M . Corticosteroid-serotonin interactions in the neurobiological mechanisms of stress-related disorders. Neurosci Biobehav Rev. 2008; 32(6):1174-84. DOI: 10.1016/j.neubiorev.2008.04.006. View

15.

Gutknecht L, Waider J, Kraft S, Kriegebaum C, Holtmann B, Reif A . Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice. J Neural Transm (Vienna). 2008; 115(8):1127-32. DOI: 10.1007/s00702-008-0096-6. View

16.

Alenina N, Kikic D, Todiras M, Mosienko V, Qadri F, Plehm R . Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc Natl Acad Sci U S A. 2009; 106(25):10332-7. PMC: 2700938. DOI: 10.1073/pnas.0810793106. View

17.

Jansen F, Heiming R, Lewejohann L, Touma C, Palme R, Schmitt A . Modulation of behavioural profile and stress response by 5-HTT genotype and social experience in adulthood. Behav Brain Res. 2009; 207(1):21-9. DOI: 10.1016/j.bbr.2009.09.033. View

18.

Chrousos G, Kino T . Glucocorticoid signaling in the cell. Expanding clinical implications to complex human behavioral and somatic disorders. Ann N Y Acad Sci. 2009; 1179:153-66. PMC: 2791367. DOI: 10.1111/j.1749-6632.2009.04988.x. View

19.

Kriegebaum C, Song N, Gutknecht L, Huang Y, Schmitt A, Reif A . Brain-specific conditional and time-specific inducible Tph2 knockout mice possess normal serotonergic gene expression in the absence of serotonin during adult life. Neurochem Int. 2010; 57(5):512-7. DOI: 10.1016/j.neuint.2010.06.015. View

20.

Baudry A, Mouillet-Richard S, Schneider B, Launay J, Kellermann O . miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science. 2010; 329(5998):1537-41. DOI: 10.1126/science.1193692. View