Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats
Serotonin is synthetized through the action of tryptophan hydroxylase (TPH) enzymes. While the TPH2 isoform is responsible for the production of serotonin in the brain, TPH1 is expressed in peripheral organs. Interestingly, despite its peripheral localization, alterations of the gene coding for TPH1...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4941 |
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| author | Giulia Sbrini Sabrina I. Hanswijk Paola Brivio Anthonieke Middelman Michael Bader Fabio Fumagalli Natalia Alenina Judith R. Homberg Francesca Calabrese |
| author_facet | Giulia Sbrini Sabrina I. Hanswijk Paola Brivio Anthonieke Middelman Michael Bader Fabio Fumagalli Natalia Alenina Judith R. Homberg Francesca Calabrese |
| author_sort | Giulia Sbrini |
| collection | DOAJ |
| description | Serotonin is synthetized through the action of tryptophan hydroxylase (TPH) enzymes. While the TPH2 isoform is responsible for the production of serotonin in the brain, TPH1 is expressed in peripheral organs. Interestingly, despite its peripheral localization, alterations of the gene coding for TPH1 have been related to stress sensitivity and an increased susceptibility for psychiatric pathologies. On these bases, we took advantage of newly generated TPH1<sup>−/−</sup> rats, and we evaluated the impact of the lack of peripheral serotonin on the behavior and expression of brain plasticity-related genes under basal conditions and in response to stress. At a behavioral level, TPH1<sup>−/−</sup> rats displayed reduced anxiety-like behavior. Moreover, we found that neuronal activation, quantified by the expression of <i>Bdnf</i> and the immediate early gene <i>Arc</i> and transcription of glucocorticoid responsive genes after 1 h of acute restraint stress, was blunted in TPH1<sup>−/−</sup> rats in comparison to TPH1<sup>+/+</sup> animals. Overall, we provided evidence for the influence of peripheral serotonin levels in modulating brain functions under basal and dynamic situations. |
| first_indexed | 2024-03-10T04:04:58Z |
| format | Article |
| id | doaj.art-0d32b3b54d2345e5964bbdd298267006 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:04:58Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0d32b3b54d2345e5964bbdd2982670062023-11-23T08:24:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239494110.3390/ijms23094941Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in RatsGiulia Sbrini0Sabrina I. Hanswijk1Paola Brivio2Anthonieke Middelman3Michael Bader4Fabio Fumagalli5Natalia Alenina6Judith R. Homberg7Francesca Calabrese8Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, 6525 EN Nijmegen, The NetherlandsDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, 6525 EN Nijmegen, The NetherlandsMax-Delbrück-Center for Molecular Medicine (MDC), 13125 Berlin, GermanyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyMax-Delbrück-Center for Molecular Medicine (MDC), 13125 Berlin, GermanyDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, 6525 EN Nijmegen, The NetherlandsDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalySerotonin is synthetized through the action of tryptophan hydroxylase (TPH) enzymes. While the TPH2 isoform is responsible for the production of serotonin in the brain, TPH1 is expressed in peripheral organs. Interestingly, despite its peripheral localization, alterations of the gene coding for TPH1 have been related to stress sensitivity and an increased susceptibility for psychiatric pathologies. On these bases, we took advantage of newly generated TPH1<sup>−/−</sup> rats, and we evaluated the impact of the lack of peripheral serotonin on the behavior and expression of brain plasticity-related genes under basal conditions and in response to stress. At a behavioral level, TPH1<sup>−/−</sup> rats displayed reduced anxiety-like behavior. Moreover, we found that neuronal activation, quantified by the expression of <i>Bdnf</i> and the immediate early gene <i>Arc</i> and transcription of glucocorticoid responsive genes after 1 h of acute restraint stress, was blunted in TPH1<sup>−/−</sup> rats in comparison to TPH1<sup>+/+</sup> animals. Overall, we provided evidence for the influence of peripheral serotonin levels in modulating brain functions under basal and dynamic situations.https://www.mdpi.com/1422-0067/23/9/4941serotonintryptophan hydroxylaseacute stressrestraint stressBdnfTPH1 |
| spellingShingle | Giulia Sbrini Sabrina I. Hanswijk Paola Brivio Anthonieke Middelman Michael Bader Fabio Fumagalli Natalia Alenina Judith R. Homberg Francesca Calabrese Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats International Journal of Molecular Sciences serotonin tryptophan hydroxylase acute stress restraint stress Bdnf TPH1 |
| title | Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats |
| title_full | Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats |
| title_fullStr | Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats |
| title_full_unstemmed | Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats |
| title_short | Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats |
| title_sort | peripheral serotonin deficiency affects anxiety like behavior and the molecular response to an acute challenge in rats |
| topic | serotonin tryptophan hydroxylase acute stress restraint stress Bdnf TPH1 |
| url | https://www.mdpi.com/1422-0067/23/9/4941 |
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