Introduction: Major depressive disorder is a mental disease with complex pathogenesis and treatment mechanisms involving changes in both the gut microbiota and neuroinflammation. Cuscutae Semen (CS), also known as Chinese Dodder seed, is a medicinal herb that exerts several pharmacological effects. These include neuroprotection, anti-neuroinflammation, the repair of synaptic damage, and the alleviation of oxidative stress. However, whether CuscutaeSemen exerts an antidepressant effect remains unknown.Methods: In this study, we evaluated the effect of CS on chronic unpredictable stress (CUS)-induced depression-like behaviors in mice by observing changes in several inflammatory markers, including proinflammatory cytokines, inflammatory proteins, and gliocyte activation. Meanwhile, changes in the gut microbiota were analyzed based on 16 S rRNA sequencing results. Moreover, the effect of CS on the synaptic ultrastructure was detected by transmission electron microscopy.Results: We found that the CS extract was rich in chlorogenic acid and hypericin. And CS relieved depression-like behaviors in mice exposed to CUS. Increased levels of cytokines (IL-1β and TNF-α) and inflammatory proteins (NLRP3, NF-κB, and COX-2) induced by CUS were reversed after CS administration. The number of astrocytes and microglia increased after CUS exposure, whereas they decreased after CS treatment. Meanwhile, CS could change the structure of the gut microbiota and increase the relative abundance of Lactobacillus. Moreover, there was a significant relationship between several Lactobacilli and indicators of depression-like behaviors and inflammation. There was a decrease in postsynaptic density after exposure to CUS, and this change was alleviated after CS treatme.Conclusion: This study found that CS treatment ameliorated CUS-induced depression-like behaviors and synaptic structural defects in mice via the gut microbiota-neuroinflammation axis. And chlorogenic acid and hypericin may be the main active substances for CS to exert antidepressant effects.

Inherent hemispheric asymmetry is important for cognition, language and other functions. Describing normal brain and asymmetry development during early development will improve our understanding of how different hemispheres prioritize specific functions, which is currently unknown. Here, we analysed developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy. We found that during this period, the difference in expression between gestational weeks (GWs) increased, and the difference in asymmetric expression decreased. Changes in the patterns of protein expression differed in the bilateral frontal lobes. Our results show that brain asymmetry can be observed in early development. These findings can guide researchers in further investigations of the mechanisms of brain asymmetry. We propose that both sides of the brain should be analysed separately in future multiomics and human brain mapping studies.

Hemispheric asymmetry is an important feature of the human brain that develops before birth. The inherent asymmetry of the brain is of great significance for cognition, language and other functions in humans. An understanding of normal brain and asymmetry development in the earliest period will further our understanding of how the different hemispheres prioritize specific functions. However, the core genetic mechanism is still unknown. Here, we analysed the developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy. We found that during this period, the difference in expression between gestational weeks (GWs) increased, and the difference in asymmetric expression decreased. The patterns of protein expression changes in the bilateral frontal lobes were different. Our results show that brain asymmetry can be observed in the early stage of foetal development. Human brain asymmetry is the result of differential gene expression before birth in the early foetal stage and develops before functional asymmetry. Researchers can use these findings to further investigate the mechanisms of brain asymmetry. We propose that both sides of the brain should be analysed separately in future multiomics research and human brain mapping studies.