Abstract
More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague–Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC–MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5β-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses.
Highlights
As a common mental disorder worldwide, depression has affected more than 300 million people of all ages globally (World Health Organization (WHO), 2019), causing heavy financial burden on families and the society
Student's t-test results indicated that the sucrose preference in MMS and F-Maternal separation (MS) group significantly decreased relative to that in the
The behavioral test results showed that sucrose preference (%) significantly decreased compared with the NMS group, indicating that MS contributed to anhedonia in SD rats
Summary
As a common mental disorder worldwide, depression has affected more than 300 million people of all ages globally (World Health Organization (WHO), 2019), causing heavy financial burden on families and the society. Children under the influence of earlylife stress (ELS), including childhood abuse and parental neglect, have considerably high probabilities of developing emotional and mental illnesses (Anacker et al, 2014; Menard et al, 2016), including anxiety and depression (Targum and Nemeroff, 2019; United States Centers for Disease Control and Prevention, 2019). Maternal separation (MS), as an ELS event model for rodents, indicates that pups exposed to MS environment display passive– submissive behavior and passively cope with stressful behavior during adulthood (Gardner et al, 2005), have long-term disruption on neural development, and may underlie vulnerability to depression (Hanson et al, 2012; Stuart et al, 2019; Zheng et al, 2019)
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