Sigma-1 Receptor: a new player of pathogenesis and therapy in cardiometabolic diseases?

The following research activities were carried out during the reporting period:

• in collaboration with WelabBarcelona, Spain, a biological material transfer agreement was signed for the purchase of biological material (Sigma-1 receptor knockout mice and their littermates) to provide the project with the necessary number of animals for experiments, as well as a colony of mice was received and breeding was initiated;
• the permit No. 133/2022 (starting from 10.04.2022) was obtained to perform experimental procedures within the framework of the project in accordance with the guidelines provided by EU Directive 2010/63/EU and in accordance with local laws and policies; all procedures have been approved by the Animal Protection Ethics Committee of the Food and Veterinary Service of Latvia in Riga, Latvia.

Publication date 05.07.2022

• The following research activities were carried out during the reporting period:
  the experiments were conducted to find out the sex-specific role of Sig1R in heart function under normal and stress conditions;
• Dr.med. Līga Zvejniece participated in symposium “Mitochondria-associated membranes as therapeutic target in rare neurodegenerative diseases” SIRMAMTHERA’22 with a lecture “Metabolomic Signatures of Sigma-1 Receptor Knockout Mice” and conducted a session “Signalling & Processes”. The event took place on October 26–27, 2022 in Bratislava, Slovakia. During the symposium, joint cooperation on Horizon Europe projects related to rare disease research was discussed.

Publication date 03.01.2023

The following research activities were carried out during the reporting period:

• the experiments were conducted to find out the sex-specific role of Sig1R in cardiometabolic function under normal and stress conditions;
• using Sig1R knockout gene models, the functional and anatomical parameters of the heart were assessed. The results were published:
  • Degtjarjovs N, Vilskersts R. The Sex-Dependent Role of Sigma-1 Receptor in Left Ventricular Function of the Mice Heart. RSU International Student Conference 2023, 27-28 March 2023, Rīga Stradiņš University, Riga, Latvia
  • Zvejniece L, Degtjarjovs N, Švalbe B, Cīrule H, Vilšķērsts R and Dambrova M. Genetic inactivation of the Sigma-1 receptor in mice alters heart function in a sex-specific manner. 5th World Congress of Latvian Scientists “Research Latvia”, 27th–29th June 2023, Riga, Latvia.

Publication date 04.07.2023

The following research activities were carried out during the reporting period:

• the experiments were conducted to find out the sex-specific role of Sig1R in cardiometabolic function under normal and stress conditions
• Gundega Stelfa defended her PhD thesis: “Experimental Models for Preclinical Investigations of Novel Drugs for Traumatic Brain Injury”, 12.2023. The thesis included research on the role of the Sigma-1 receptor during the post-trauma period (doi: 10.3390/ijms222111611.).
• As part of the Consolidation of the Latvian Institute of Organic Synthesis and the Latvian Biomedical Research and Study Centre initiative, Liga Zvejniece prepared and submitted a research project proposal titled: “Transcriptome Analysis in Specific Brain Regions of Sigma-1 Receptor Knockout Mice.” The proposal was submitted in October 2023 and received positive approval in December 2023.
• Liga Zvejniece, in collaboration with leading European colleagues engaged in Sigma-1 receptor research, prepared and submitted a project proposal to the COST Association, European Cooperation in Science & Technology. The project, titled “European Network for Sigma-1 Receptor as a Therapeutic Opportunity” (SIGMA-1 EUROPE), was submitted on October 19, 2023.
• Young scientists E. Viluma, A. Novosada, and N. Degtjarjovs participated in the Researchers’ Night event (September 2023), promoting science and providing detailed insights to attendees about the role of the Sigma-1 receptor in physiology and pathology.
• using Sig1R knockout gene models, the functional and anatomical parameters of the heart were assessed. The results were disseminated: 

• L Zvejniece, A Novosada, E Viluma, N Degtjarjovs, E Liepinsh, R Vilskersts, M Dambrova. Sex-specific roles of Sig1R in cardiometabolic function and stress response. 4th European Symposium, Physiopathology of Sigma-1 Receptors, 28-30 September 2023, Montpelier, France.  Oral Presentation. 
• N Degtjarjovs, A Novosada, E Viluma, B Svalbe, H Cirule, L Zvejniece, E Liepinsh, R Vilskersts, M Dambrova.  Male but not female Sigma-1 Receptor knockout mice have altered cardio function. 4th European Symposium, Physiopathology of Sigma-1 Receptors, 28-30 September 2023, Montpelier, France.  Poster Presentation. 
• E Viluma, A Novosada, M Dambrova, L Zvejniece.  Exploring the role of Sig1R in metabolic Syndrome: Sex-dependent findings in murine models. 4th European Symposium, Physiopathology of Sigma-1 Receptors, 28-30 September 2023, Montpelier, France.  Poster Presentation. 

Publication date 11.01.2024

The following research activities were carried out during the reporting period:

• the experiments were conducted to find out the sex-specific role of Sig1R in cardiometabolic function under normal and stress conditions
• As part of the collaboration with Riga Stradiņš University, the role of the Sigma-1 receptor in cardiac tissues was investigated using electron microscopy.
• Ennata Viluma defended her Master’s thesis: “Sigma-1 receptor knockout mice are protected from high-fat diet-induced insulin resistance “, 05.2024. 
• N Degtjarjovs defended his Master’s thesis: “Loss of the Sigma-1 receptor exacerbates heart failure in a sex-specific manner”, 05.2024.
• The project, titled “European Network for Sigma-1 Receptor as a Therapeutic Opportunity” (SIGMA-1 EUROPE), was accepted in COST Action on May, 2024.
• Submitted manuscript. Stelfa G, Miteniece A, Svalbe B, Vavers E, Makrecka-Kuka M, Kupats E, Kunrade L, Parfejevs V, Riekstina U, Dambrova M, Zvejniece L. Age-dependent changes in visceral adiposity are associated with decreased plasma levels of DHEA-S in sigma-1 receptor knockout male mice” in Journal Biochim Biophys Acta Mol Cell Biol Lipids.

Publication date 12.07.2024

The following research activities were carried out during the reporting period:

• the experiments were conducted to find out the sex-specific role of Sig1R in cardiometabolic function under normal and stress conditions
• Young scientist E. Viļuma participated in the Researchers’ Night event (September 2024), promoting science and providing detailed insights to attendees about the role of the Sigma-1 receptor in physiology and pathology.
• At the first MC meeting in Brisele (October 2024), L.Zvejniece was elected as a Vice-Chair of the COST action SIGMA-1 EUROPE.
• Submitted manuscript. Vilskersts R, Degtjarjovs N, Novosada A, Viluma E, Svalbe B, Cirule H, Pinkovskis K, Groma V, Skuja S, Briviba M, Saksis R, Liepinsh E, Dambrova M, Zvejniece L.   “Genetic inactivation of the Sigma-1 receptor in mice alters heart function in a sex-specific manner” in Journal Biology of Sex Differences. 

• Submitted manuscript. Cagalinec M, Delprat B, Adnan M, Borecka S, Bultynck G; Choubey V; Yanovsky-Dagan S; Ezer S; Gasperikova D; Harel T, Jurkovicova D; Kaasik A; Lievens JC; Maurice T; Peviani M; Richard EM, Skoda J, Skopkova M, Tarot P, Van Gorp R, Zvejniece L. Review Article. Improving mitochondria-associated membranes integrity as converging therapeutic strategy for rare neurodegenerative diseases and cancer. In Journal BBA– Molecular Cell Research. 

• Accepted manuscript. Stelfa G, Miteniece A, Svalbe B, Vavers E, Makrecka-Kuka M, Kupats E, Kunrade L, Parfejevs V, Riekstina U, Dambrova M, Zvejniece L. Age-dependent changes in visceral adiposity are associated with decreased plasma levels of DHEA-S in sigma-1 receptor knockout male mice” in Journal Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jan;1870(1):159571 (DOI: 10.1016/j.bbalip.2024.159571). 
• Submitted manuscript (in latvian).  Ennata Viļuma un Līga Zvejniece. Sigma-1 receptors: loma slimību patoģenēzē un zāļu vielu izpētes perspektīvas (Sigma-1 receptor: Role in disease pathogenesis and prospects for drug research). Medicus Bonus, 2025.

Publication date 12.01.2025