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−/− 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−/− rats displayed reduced anxiety-like behavior. Moreover, we found that neuronal activation, quantified by the expression of Bdnf and the immediate early gene Arc and transcription of glucocorticoid responsive genes after 1 h of acute restraint stress, was blunted in TPH1−/− rats in comparison to TPH1+/+ animals. Overall, we provided evidence for the influence of peripheral serotonin levels in modulating brain functions under basal and dynamic situations.

Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats / G. Sbrini, S.I. Hanswijk, P. Brivio, A. Middelman, M. Bader, F. Fumagalli, N. Alenina, J.R. Homberg, F. Calabrese. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:9(2022 Apr 29), pp. 4941.1-4941.14. [10.3390/ijms23094941]

Peripheral Serotonin Deficiency Affects Anxiety-like Behavior and the Molecular Response to an Acute Challenge in Rats

G. Sbrini
Primo
;
P. Brivio;F. Fumagalli;F. Calabrese
2022

Abstract

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−/− 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−/− rats displayed reduced anxiety-like behavior. Moreover, we found that neuronal activation, quantified by the expression of Bdnf and the immediate early gene Arc and transcription of glucocorticoid responsive genes after 1 h of acute restraint stress, was blunted in TPH1−/− rats in comparison to TPH1+/+ animals. Overall, we provided evidence for the influence of peripheral serotonin levels in modulating brain functions under basal and dynamic situations.
acute stress; Bdnf; restraint stress; serotonin; TPH1; tryptophan hydroxylase;
Settore BIO/14 - Farmacologia
   Antidepressant drugs effect on the gender-dependent development of depressive behavior induced by early neuroinflammatory hit: a multitask approach from mice to patients
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   201779W93T_002

   Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
29-apr-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/925554
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