TY - JOUR

T1 - Expression Profiles of Genes Related to Serotonergic Synaptic Function in Hypothalamus of Hypertensive and Normotensive Rats in Basal and Stressful Conditions

AU - Redina, Olga E.

AU - Ryazanova, Marina A.

AU - Oshchepkov, Dmitry Yu.

AU - Makovka, Yulia V.

AU - Markel, Arcady L.

N1 - The transcriptomic analysis was funded by the Russian Science Foundation, grant number 22-14-00082. The use of computational resources of the Multi-Access Center “Bioinformatics” (Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia) was supported by the Russian government project FWNR-2022-0020. Breeding, regular care and maintenance of experimental rats in the Vivarium for conventional animals (Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia) was supported by the state project of the Russian Federation FWNR-2022-0019. Expression Profiles of Genes Related to Serotonergic Synaptic Function in Hypothalamus of Hypertensive and Normotensive Rats in Basal and Stressful Conditions / Olga E. Redina, Marina A. Ryazanova, Dmitry Y. Oshchepkov, Yulia V. Makovka, Arcady L. Markel // International Journal of Molecular Sciences. – 2025. – Vol. 26, No. 15. № 7058. – DOI 10.3390/ijms26157058.

PY - 2025/7/22

Y1 - 2025/7/22

N2 - The hypothalamus belongs to the central brain structure designed for the neuroendocrine regulation of many organismal functions, including the stress response, cardiovascular system, and blood pressure, and it is well known that the serotonergic hypothalamic system plays a significant role in these processes. Unfortunately, the genetic determination of serotonergic hypothalamic mechanisms has been little studied. The aim of this article is to describe the expression profile of the genes in the hypothalamic serotonergic synapses in hypertensive ISIAH rats in comparison with normotensive WAG rats in control conditions and under the influence of a single short-term restraint stress. It was found that 14 differentially expressed genes (DEGs) may provide the inter-strain differences in the serotonergic synaptic function in the hypothalamus between the hyper- and normotensive rats studied. In hypertensive rats, downregulation of Slc18a1 gene in the presynaptic serotoninergic ends and decreased expression of Cacna1s and Htr3a genes determining the postsynaptic membrane conductance may be considered as a main factors causing differences in the function of hypothalamic serotoninergic synapses in hypertensive ISIAH and normotensive WAG rats at the basal conditions. Under basal conditions, glial cell genes were not involved in the formation of inter-strain differences in serotonergic synaptic function. The analysis of transcriptional responses to restraint stress revealed key genes whose expression is involved in the regulation of serotonergic signaling, and a cascade of interrelated changes in biological processes and metabolic pathways. Stress-dependent changes in the expression of some DEGs are similar in the hypothalamus of hypertensive and normotensive rats, but the expression of a number of genes changes in a strain-specific manner. The results suggest that in hypothalamic glial cells of both strains, restraint stress induces changes in the expression of DEGs associated with the synthesis of Ip3 and its receptors. Many of the identified serotonergic DEGs participate in the regulation of not only serotonergic synapses but may also be involved in the regulation of cholinergic, GABAergic, glutamatergic, and dopaminergic synapses. The results of the study provide new information on the genetic mechanisms of inter-strain differences in the functioning of the hypothalamic serotonergic system in hypertensive ISIAH and normotensive WAG rats at rest and under the influence of a single short-term restraint (emotional) stress.

AB - The hypothalamus belongs to the central brain structure designed for the neuroendocrine regulation of many organismal functions, including the stress response, cardiovascular system, and blood pressure, and it is well known that the serotonergic hypothalamic system plays a significant role in these processes. Unfortunately, the genetic determination of serotonergic hypothalamic mechanisms has been little studied. The aim of this article is to describe the expression profile of the genes in the hypothalamic serotonergic synapses in hypertensive ISIAH rats in comparison with normotensive WAG rats in control conditions and under the influence of a single short-term restraint stress. It was found that 14 differentially expressed genes (DEGs) may provide the inter-strain differences in the serotonergic synaptic function in the hypothalamus between the hyper- and normotensive rats studied. In hypertensive rats, downregulation of Slc18a1 gene in the presynaptic serotoninergic ends and decreased expression of Cacna1s and Htr3a genes determining the postsynaptic membrane conductance may be considered as a main factors causing differences in the function of hypothalamic serotoninergic synapses in hypertensive ISIAH and normotensive WAG rats at the basal conditions. Under basal conditions, glial cell genes were not involved in the formation of inter-strain differences in serotonergic synaptic function. The analysis of transcriptional responses to restraint stress revealed key genes whose expression is involved in the regulation of serotonergic signaling, and a cascade of interrelated changes in biological processes and metabolic pathways. Stress-dependent changes in the expression of some DEGs are similar in the hypothalamus of hypertensive and normotensive rats, but the expression of a number of genes changes in a strain-specific manner. The results suggest that in hypothalamic glial cells of both strains, restraint stress induces changes in the expression of DEGs associated with the synthesis of Ip3 and its receptors. Many of the identified serotonergic DEGs participate in the regulation of not only serotonergic synapses but may also be involved in the regulation of cholinergic, GABAergic, glutamatergic, and dopaminergic synapses. The results of the study provide new information on the genetic mechanisms of inter-strain differences in the functioning of the hypothalamic serotonergic system in hypertensive ISIAH and normotensive WAG rats at rest and under the influence of a single short-term restraint (emotional) stress.

KW - Animals

KW - Hypothalamus/metabolism

KW - Rats

KW - Hypertension/genetics

KW - Male

KW - Serotonin/metabolism

KW - Synapses/metabolism

KW - Gene Expression Profiling

KW - Stress, Psychological/genetics

KW - Transcriptome

KW - Stress, Physiological/genetics

KW - Serotonergic Neurons/metabolism

KW - Blood Pressure

UR - https://www.mendeley.com/catalogue/ee894908-7f2a-36eb-9e8d-d066733be489/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105013362633&origin=inward

UR - https://pubmed.ncbi.nlm.nih.gov/40806189/

U2 - 10.3390/ijms26157058

DO - 10.3390/ijms26157058

M3 - Article

C2 - 40806189

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 15

M1 - 7058

ER -