TY - JOUR

T1 - Effect of Short-Term Restraint Stress on the Hypothalamic Transcriptome Profiles of Rats with Inherited Stress-Induced Arterial Hypertension (ISIAH) and Normotensive Wistar Albino Glaxo (WAG) Rats

AU - Oshchepkov, Dmitry Yu

AU - Makovka, Yulia V.

AU - Fedoseeva, Larisa A.

AU - Seryapina, Alisa A.

AU - Markel, Arcady L.

AU - Redina, Olga E.

N1 - The authors are thankful to the multi-access center Bioinformatics for the use of computational resources (Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia) as supported by the Russian government project FWNR-2022-0020. The authors are also grateful to the Vivarium for Conventional Animals (Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia) for the breeding, regular care, and maintenance of the experimental rats, as supported by Russian government project FWNR-2022-0019. The authors are grateful to the Institute of Genomic Analysis (Moscow, Russia) for technical assistance in conducting the study and BGI Hongkong Tech Solution NGS Lab for conducting the technological part of the experiment. The study was supported by the Russian Science Foundation (grant No. 22-14-00082).

PY - 2024/6

Y1 - 2024/6

N2 - Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes in the transcriptome profiles of the hypothalamus of hypertensive ISIAH and normotensive WAG rats exposed to a single short-term restraint stress (the rat was placed in a tight wire-mesh cage for 2 h). This type of stress can be considered emotional stress. The functional annotation of differentially expressed genes allowed us to identify the most significantly altered biological processes in the hypothalamus of hypertensive and normotensive rats. The study made it possible to identify a group of genes that describe a general response to stress, independent of the rat genotype, as well as a hypothalamic response to stress specific to each strain. The alternatively changing expression of the Npas4 (neuronal PAS domain protein 4) gene, which is downregulated in the hypothalamus of the control WAG rats and induced in the hypothalamus of hypertensive ISIAH rats, is suggested to be the key event for understanding inter-strain differences in the hypothalamic response to stress. The stress-dependent ISIAH strain-specific induction of Fos and Jun gene transcription may play a crucial role in neuronal activation in this rat strain. The data obtained can be potentially useful in the selection of molecular targets for the development of pharmacological approaches to the correction of stress-induced pathologies related to neuronal excitability, taking into account the hypertensive status of the patients.

AB - Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes in the transcriptome profiles of the hypothalamus of hypertensive ISIAH and normotensive WAG rats exposed to a single short-term restraint stress (the rat was placed in a tight wire-mesh cage for 2 h). This type of stress can be considered emotional stress. The functional annotation of differentially expressed genes allowed us to identify the most significantly altered biological processes in the hypothalamus of hypertensive and normotensive rats. The study made it possible to identify a group of genes that describe a general response to stress, independent of the rat genotype, as well as a hypothalamic response to stress specific to each strain. The alternatively changing expression of the Npas4 (neuronal PAS domain protein 4) gene, which is downregulated in the hypothalamus of the control WAG rats and induced in the hypothalamus of hypertensive ISIAH rats, is suggested to be the key event for understanding inter-strain differences in the hypothalamic response to stress. The stress-dependent ISIAH strain-specific induction of Fos and Jun gene transcription may play a crucial role in neuronal activation in this rat strain. The data obtained can be potentially useful in the selection of molecular targets for the development of pharmacological approaches to the correction of stress-induced pathologies related to neuronal excitability, taking into account the hypertensive status of the patients.

KW - ISIAH rat strain

KW - RNA-Seq

KW - gene expression

KW - hypertension

KW - hypothalamus

KW - short-term restraint stress

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85197125164&origin=inward&txGid=fb42727e1e2db7529029ba7adc826c26

UR - https://www.mendeley.com/catalogue/4a325d00-cc9f-3fcb-a109-2536474099d4/

U2 - 10.3390/ijms25126680

DO - 10.3390/ijms25126680

M3 - Article

C2 - 38928385

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 12

M1 - 6680

ER -