PhD Scientific Days 2023

Pharmaceutical Sciences - Posters F

Exploring the Effects of Citalopram on Gene Expression and the Serotonergic Receptor Pathway: A Neuroendocrine Challenge Study

Előadó neve

Dr. Kumar, Sahel

Neptun code

U92011

Előadó munkahelye

Department of Pharmacodynamics, Semmelweis University

Előadó telefonszáma

+491724182089

Előadó e-mail címe

sahel.kumar@gmail.com

Az előadás címe

Exploring the Effects of Citalopram on Gene Expression and the Serotonergic Receptor Pathway: A Neuroendocrine Challenge Study

Szerző(k) neve és munkahelye

Sahel Kumar1,2,3, Kinga Gecse1,2,3, Daniel Baksa1,2,3, Gyorgy Bagdy1,2,3, Gabriella Juhasz1,2,3, Peter Petschner1,2,3,4

1Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
2SE-NAP2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.
3NAP-3.0-SE Neuropsychopharmacology Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.
4Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan.

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences - Posters F

Language of the presentation

English

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction:
Citalopram (CIT) can cause heightened arousal and activate the stress response system, leading to increased release of prolactin, ACTH, and cortisol through the HPA axis. It is used as a neuroendocrine challenge to evaluate the body's stress response. While previous studies have investigated the effects of this challenge on plasma levels, neuroimaging, and behavior, to our knowledge gene-expression studies have not been conducted yet.

Aims:
This study aimed to use gene-expression measurements during CIT neuroendocrine challenge in humans to provide new insights or confirm previous findings.

Method:
The study recruited 52 subjects without acute or chronic illnesses except for migraines and no medication intake. Two blood samples were taken with the first serving as a baseline measurement. Participants were then infused with 7.5mg CIT, and a second sample was taken 60 minutes later. RNA-sequencing was used to measure gene-expression, followed by statistical analysis using edgeR in R. Lastly, pathway-level analysis was conducted using the R package fgsea.

Results:
Our findings suggest no differentially expressed genes after multiple hypothesis correction in the CIT-administered data compared to the baseline. However, several pathways showed differential expressions, including the negatively enriched Serotonin Receptor 4/6/7 and NR3C1 Signaling (WP734) pathway (adjusted p-value: 0.005 | Normalized enrichment score: -1.73).

Conclusion:
This human gene expression study of the CIT challenge showed early downregulation of the serotonergic 4/6/7 receptor pathway, leading to the downregulation of the glucocorticoid receptor (NR3C1) in the periphery. This suggests an early body reaction to elevated serotonin levels, which may also be present in the brain. This pathway level change could serve as a biomarker to indicate alterations in various patient groups and treatment response. However, further research is required to explore this potential biomarker.

Funding:
Development of scientific workshops of medical, health sciences and pharmaceutical
educations (EFOP-3.6.3-VEKOP-16-2017-00009); ÚNKP-22-3-II-SE-27; 2017-1.2.1-NKP-2017-00002,NAP2022-I-4/2022; TKP2021-EGA-25; OTKA (K143391); ERA PerMed (2019-2.1.7-ERA-NET-2020-00005). PP is a Research Fellow of the Japan Society for the Promotion of Science under the Postdoctoral Fellowships for Research in Japan (Standard) P20809.

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. Peter Petschner

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6837

Start

11:24

End

11:29

Authors (legacy)

Sahel Kumar1,2,3, Kinga Gecse1,2,3, Daniel Baksa1,2,3, Gyorgy Bagdy1,2,3, Gabriella Juhasz1,2,3, Peter Petschner1,2,3,4

1Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
2SE-NAP2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.
3NAP-3.0-SE Neuropsychopharmacology Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.
4Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan.