Our research goal is to understand the synaptic mechanisms involved in the pathophysiology of chronic pain and psychiatric disorders. We try to understand how brain circuit modulates neuronal transmission in midbrain periaqueductal gray, which is an critical region of midbrain for controlling of pain and emotion. We also try to understand how the analgesic compounds and antidepressants regulate pain and depression leads to therapeutic efficacy in the brain, especially in the periaqueductal gray.
Statement of the Problem: Major depressive disorder affecting more than 100 million people worldwide every year is a heterogeneous illness. To date, current pharmacotherapies require prolonged administration from several weeks to months for an appreciable response. This is particularly concerning given that suicide risk is elevated in subjects with depression. Methodology & Theoretical Orientation: It is still unclear that whether ketamine metabolite (2R,6R-hydroxynorketamine; 2R,6R-HNK) rescues chronic stress-elicited depression-like behavior. Depression-like behavior in the rats were induced by learned helplessness (LH) procedure. Forced swim test (FST) and sucrose preference test (SPT) were used to study the depression-like behavior. Findings: Rats receiving learned helplessness procedure exhibited high failure rate in the escapable footshock test compared to control group. LH rats exhibited an increase in immobile time during the FST and a reduction in sucrose consumption. Intraperitoneal ketamine metabolite, 2R,6R-HNK, injection decreased immobile time during the FST and increased sucrose consumption in LH rats. Conclusion & Significance: Ketamine metabolite 2R,6R-HNK rescues LH-induced depression-like behavior including despair behavior and anhedonia. These results may pave the foundation for a critical issue that ketamine metabolite, 2R,6R-HNK plays crucial roles in stress-induced depression-like behaviors and provides a new insight into depression management and development of antidepressants.
Yuhong Guo, who received a bachelor's degree from Hunan Medical Sciences University (1994-1999), has his expertise in studying traditional Chinses herbal medicines on ICU diseases. She also engaged in pathogenesis of sepsis, psoriasis, and inflammatory diseases. She is now continuing her research work in Beijing Hospital of Traditonal Chinese Medicine and Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases.
Sepsis is reported to be an unusual systemic reaction to infection, accompanied by multiple-organ failure. Sepsis-induced cardiomyopathy, defined as damages and dysfunction of the heart, is essential in the pathogenesis of sepsis. Traditional Chinese formula, which has long been used to improve the situation of patients through multitarget regulation, is now gradually being used as complementary therapy. The present study aimed to investigate the effect of Qiang-Xin 1 (QX1) formula, a traditional Chinese herbal medicine designed for cardiac dysfunction, on cecal ligation puncture (CLP)-induced heart damage and its underlying mechanisms in mice. Survival test first showed that an oral administration of QX1 formula significantly increased the 7-day survival of septic mice from 22% to 40%. By estimating the secretion of serum cytokines, QX1 treatment dramatically inhibited the excessive production of interleukin-1β and tumor necrosis factor-α. Immunohistochemical staining illustrated that the expression of c-Jun N-terminal kinase, caspase-12, and high-mobility group box 1 was downregulated in cardiomyocytes of the QX1-treated group compared with that of the CLP surgery group. Western blotting confirmed that the activation of essential caspase family members, such as caspase-3, caspase-9, and caspase-12, was prohibited by treatment with QX1. Moreover, the abnormal expression of key regulators of endoplasmic reticulum and mitochondria-associated apoptosis in cardiomyocytes of septic mice, including CHOP, GRP78, Cyt-c, Bcl-2, Bcl-XL, and Bax, was effectively reversed by treatment with QX1 formula. This study provided a new insight into the role of QX1 formula in heart damage and potential complementary therapeutic effect of traditional Chinese medicine on sepsis.