Emotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior.

Sepsis is defined as a life-threatening organ dysfunction caused by excessive formation of reactive oxygen species (ROS) and dysregulated inflammatory response. Previous studies have reported that shikonin (Shik) possess prominent anti-inflammatory and antioxidant effects and holds promise as a potential therapeutic drug for sepsis. However, the poor water solubility and the relatively high toxicity of shikonin hamper its clinical application. To address this challenge, we constructed Zn²⁺-shikonin nanoparticles, hereafter Zn-Shik-PEG NPs, based on an organic-inorganic hybridization strategy of metal-polyphenol coordination to improve the aqueous solubility and biosafety of shikonin. Mechanistic studies suggest that Zn-Shik-PEG NPs could effectively clear intracellular ROS via regulating the Nrf2/HO-1 pathway, meanwhile Zn-Shik-PEG NPs could inhibit NLRP3 inflammasome-mediated activation of inflammation and apoptosis by regulating the AMPK/SIRT1 pathway. As a result, the Zn-Shik-PEG NPs demonstrated excellent therapeutic efficacies in lipopolysaccharide (LPS) as well as cecal ligation puncture (CLP) induced sepsis model. These findings suggest that Zn-Shik-PEG NPs may have therapeutic potential for the treatment of other ROS-associated and inflammatory diseases.

Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) patients. Acupuncture at different acupoints could exert different modulatory effects on the brain network. However, whether acupuncture at real or sham acupoints can produce different effects on the brain network in MCI or AD patients remains unclear. Using resting-state fMRI, we reported that acupuncture at Taixi (KI3) induced amplitude of low-frequency fluctuation (ALFF) change of different brain regions in MCI patients from those shown in the healthy controls. In MCI patients, acupuncture at KI3 increased or decreased ALFF in the different regions from those activated by acupuncture in the healthy controls. Acupuncture at the sham acupoint in MCI patients activated the different brain regions from those in healthy controls. Therefore, we concluded that acupuncture displays more significant effect on neuronal activities of the above brain regions in MCI patients than that in healthy controls. Acupuncture at KI3 exhibits different effects on the neuronal activities of the brain regions from acupuncture at sham acupoint, although the difference is only shown at several regions due to the close distance between the above points.