Perinatal serotonergic manipulation shapes anhedonic and cognitive behaviors in a sex- and age-dependent manner: Identification of related biological functions at central and peripheral level.

Autor: Gallo MT; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università Degli Studi di Milano, Milan, Italy., Brivio P; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università Degli Studi di Milano, Milan, Italy. Electronic address: paola.brivio@unimi.it., Dolci B; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università Degli Studi di Milano, Milan, Italy., Fumagalli F; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università Degli Studi di Milano, Milan, Italy., Calabrese F; Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università Degli Studi di Milano, Milan, Italy.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2023 Nov; Vol. 114, pp. 118-130. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1016/j.bbi.2023.08.016
Abstrakt: Poor knowledge about psychiatric disorders often results in similar diagnoses for patients with different symptoms, thus limiting the effectiveness of the available medications. As suggested by several lines of evidence, to improve these shortcomings, it is essential to identify biomarkers associated with specific symptoms and to stratify patients into more homogeneous populations taking a further step toward personalized medicine. Here, we aimed to associate specific behavioral phenotypes with specific molecular alterations by employing an animal model based on the pharmacological manipulation of the serotonergic system, which mimics a condition of vulnerability to develop psychiatric disorders. In particular, we treated female and male rats with fluoxetine (FLX 15 mg/kg dissolved in drinking water) during prenatal or early postnatal life, and we evaluated different pathological-like phenotypes (cognitive deficit, anhedonia, and anxiety) by exposing the rats to a battery of behavioral tests during adolescence and adulthood. In addition, we carried out molecular analyses on specific brain areas and in the blood. Our results showed that perinatal FLX administration determined age- and sex-dependent effects, with males being more sensitive to prenatal manipulation and manifesting anhedonic-like behavior and females to early postnatal exposure, exhibiting cognitive deficits and a less anxious phenotype. Furthermore, we identified, peripherally and centrally, biological functions altered by perinatal serotonin modulation regardless of the timing of exposure and sex, and other pathways specific for the pathological-like phenotypes. The results presented here provide new insights into potential biomarkers associated with specific behavioral phenotypes that may be useful for broadening knowledge about psychiatric conditions.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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