Sex-dependent differences in stress-induced depression in Wistar rats are accompanied predominantly by changes in phosphatidylcholines and sphingomyelins.

With a high annual and lifetime prevalence, depression is becoming the leading contributor to the global disease burden. During the COVID-19 crisis, the depression and mood disorders accelerated significantly. Despite the growing evidence, the precise underlying mechanisms of depression disorders (DD) remain unknown. When studying DD in humans, there are many uncontrollable factors such as medication history, age of the patient or living conditions. In this regard, animal models provide an essential step for examining neural circuitry or molecular and cellular pathways in a controlled environment. As far as we know, women have a consistently higher prevalence of DD than men. Thus, the aim of our study was to evaluate sex-related changes in blood metabolites in a model of stress-induced depression in Wistar rats. Pregnant females were stressed using restriction of mobility in the final week of the pregnancy three times a day for 45 minutes each, three following days. After the birth, the progeny aged 60 days was stressed repeatedly. The perturbation in overall energy metabolism as well as in lipid metabolism was found. While in males, phosphatidylcholines (the most phosphatidylcholine with acyl-alkyl residue sum C40:4 - PC ae C40:4), sphingomyelins, and acylcarnitines were changed, in females, lipid metabolism perturbation was seen with the most critical alteration in hydroxysphingomyelin with acyl residue sum C16:1 (SM OH C16:1). Our results confirm that the animal model may be used further in the research of depression. Our results may provide an essential insight into the sex-dependent pathogenesis of depression and contribute to the search for effective treatment and prevention of depression with respect to sex.

Defining sex differences in selected lipid metabolites of blood plasma in Wistar rats.

There is an increasing attention to the role that sex/gender plays in health, behavior and outcomes. Even though we know that males and females are not the same, experiments have sometimes been carried out without considering sex in scientific research. It is essential for scientists and clinicians to consider sex differences as one of the underlying physiological determinants of health and disease to provide the building blocks for evidence-based, individualized medicine. Our work aimed to reveal sex-associated differences in lipid metabolite levels of adult female (n = 10) and male (n = 10) Wistar rats, aged 60 days. Partial least square determination analysis (PLS-DA) method and a variance importance in projection (VIP) score was used to identify the key sex-specific metabolites. Our results show that all groups of lipid metabolites: lysophosphatidylcholines (lysoPCs), phosphatidylcholines (PCs), and sphingomyelins (SMs) show a significant sex-dependent pattern. According to our results, more than a half of lysoPCs studied showed sex-specific features. PCs and lysoPCs tend to be significantly elevated in the blood plasma of females. The most distinct increase in more than 90% of SMs has been revealed in female blood plasma, compared with males. According to VIP score, the most important feature was the metabolite PC aa C38:4. Our study points out a sex dimorphism in lipid metabolism. The identification of main lipid features may play a key role in preclinical and clinical practice.