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

July 20, 2023

Giulia Sbrini, Sabrina I. Hanswijk, Paola Brivio, Anthonieke Middelman, Michael Bader, Fabio Fumagalli, Natalia Alenina, Judith R. Homberg, Francesca Calabrese

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.

Journal: International Journal of Molecular Sciences