Backgrounds Chronic stress could induce depression-like phenotype in animal models. Previous data showed that sex differences exist after chronic stress model establishment, however, the detailed information about the difference of blood biochemical indexes is not clear. In this study, we aim to supply comparison of monoamine transmitters and related hormone markers in serum between male and female depressed mice, and in order to better understand the sex difference in transmitters and hormone levels in depression occurrence and development. Methods Sixty C57BL/6 mice (both male and female) were divided into two groups by gender. Same gender mice were then divided randomly into the non-treated control group and chronic stress group which was exposed to 8 weeks of chronic unpredictable mild stress (CUMS). Depression-like behavior was assessed with open-field test and sucrose preference test. Blood sample was collected and monoamine transmitter and related hormone in serum were measured by ELISA. Results The depression-like phenotype mice model was established successfully after 8 weeks of chronic stress. The locomotion activity scores in male stressed mice declined more than that in female stressed mice, while the exploratory behavior scores in female stressed mice declined more than that in male stressed mice. Compared to non-treated control group mice, mice in the chronic stress group in response to stress showed greater declines in monoamine transmitters (5-HT, dopamine, norepinephrine) and sex hormones (androgen, estrogen, oxytocin and prolactin), while stress hormones (adrenaline, corticosterone and ACTH) were significantly increased. The decrease of norepinephrine, androgen and estrogen in female stressed mice was greater than in male stressed mice, whereas the 5-HT and oxytocin in male stressed mice decreased more than in female stressed mice, and the corticosterone in male stressed mice increased more than in female stressed mice. Conclusion Sex differences of monoamine transmitter and related hormone levels in serum occurred in chronic stress induced depression-like phenotype mice model. It may provide a useful reference to guide precise antidepressant treatment in different gender population in clinical care.

The serotonin hypothesis of depression is still influential, but the relationship between peripheral 5-HT levels and depression is still unknown. This review aimed to verify whether peripheral 5-HT levels could be used as a biomarker for depression diagnosis and treatment. PubMed and EMBASE were searched using terms appropriate to the area of research. Articles from 1957 to 2022 in the following terms were identified: depression, 5-HT, serotonin and peripheral (serum, plasma, blood platelets). 33 studies were included: seven clinical trials about periphery 5-HT levels in depressive patients compared to normal subjects, 15 clinical trials about changes of peripheral 5-HT levels in patients with depression after drug treatment and 11 animal experiments about peripheral 5-HT levels in animal models of depression. Peripheral 5-HT levels presented three different outcomes before and after antidepressant treatments: increased, decreased and no significant change. In conclusion, changes in peripheral 5-HT levels did not show consistent results among these studies. Peripheral 5-HT level could not be used as a biomarker both for depression diagnosis and for antidepressant efficacy evaluation.

Objective: Gut microbiota play a key role in the pathogenesis of obesity and depression. Probiotics are a preventive strategy for obesity and a novel treatment for depression symptoms. However, the ameliorative or therapeutic effect of potential probiotic candidate Lactobacillus reuteri (L. reuteri) on obesity and depression comorbidity still remains unclear. We investigated the effects of chronic unpredictable mild stress (CUMS) in high-fat diet-fed mice and the effects of Lactobacillus reuteri strain 8008 on various disease indicators of obesity and depression comorbidity disease.Methods: Forty male C57BL/6 mice were randomized into 2 groups: the normal control (NC) group (n = 10) and the high-fat diet (HFD) group (n = 30), being fed with normal diet (ND) or high-fat diet (HFD) for 8 weeks, respectively. Then the obese mice fed with HFD were randomly allocated into 3 sub-groups: the HFD group (n = 10); the HFD + CUMS group (n = 10); the HFD + CUMS + L.r group (n = 10). The latter 2 subgroups underwent CUMS for 4 weeks to build the obesity and depression comorbidity mice model. During the duration of treatment, mice were gavaged with 0.5 mL PBS solution or L. reuteri (2 × 109 CFU/mL) once a day, respectively. The body weight, food intake, organ weight, behavioral indicators, histology, blood lipids, levels of inflammatory cytokines and tight junction proteins and abundance of colonic contents bacteria were measured.Results: The obesity and depression comorbidity mice model was successfully established after HFD feeding and chronic stress. The comorbid mice demonstrated inflammatory responses increase in liver and adipose tissues, worsened damage to the intestinal barrier as well as gut microbiota disorder. Gavaged with L. reuteri attenuated depressive-like behavior, improved blood lipids and insulin resistance, reduced inflammation in liver and adipose tissues, improved intestinal tight junctions as well as the microbiome dysbiosis in obesity and depression comorbidity mice.Conclusion:Lactobacillus reuteri strain 8008 could alleviate depressive-like behaviors and related indicators of obesity disorders by regulating the gut microbiota in obesity and depression comorbid mice.

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