Research Abstract:
Our major focus is to study the molecular mechanisms underlying the assembly of the spinal dorsal horn circuitry. Spinal dorsal horn is a pivotal center for integrating and relaying pain- and itch-sensing signals from the periphery to the brain. Our study have shown that several transcription factors play important functions in the formation of dorsal spinal cord and in the projections of primary afferents to the spinal cord. In addition, we have performed genome-wide profiling of the dorsal horn-enriched genes and identified potential pain- and itch-sensing genes. Recently, we have confirmed that several genes indeed have important roles in relaying pain and/or itching signals in the spinal cord, and are studying their roles using genetic, molecular, pharmacological and behavioral approaches.
Another area of our research is to study the role of the central serotonergic system in animal behavior. Serotonin (5-HT), a key neurotransmitter, has been implicated in numerous psychiatric disorders. Our study found that the transcription factor Lmx1b is critical for the development of all central 5-HT neurons. Using genetic approaches we have ablatedLmx1b-expressing 5-HT neurons in mice and are studying the role of 5-HT neurons in behaviors including pain responses, reward and depression using pharmacological and behavioral approaches.
Our multidisciplinary approaches may not only help to gain insights into molecular basis of the dorsal horn development, but also reveal potential sites of drug actions on central pain/itch pathways and thus aid in the new pharmacological strategies for pain/ and itch relief.
Selected Publications:
Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY and Chen ZF. Cellular Basis of Itch Sensation. Science 2009 Aug 6.
Sun YG and Chen ZF. Gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature 2007 448:700-703.
Zhao ZQ, Gao YJ, Sun YG, Zhao CS, Gereau RW and Chen ZF. Central serotonergic neurons are differentially required for opioid analgesia, morphine tolerance and morphine reward. Proc Natl Acad Sci USA 2007 104:14519-14524.
Zhao ZQ, Chiechio S, Sun YG, Zhang KH, Zhao CS, Scott M, Johnson R, Deneris E, Renner K, Gereau RW and Chen ZF. MIce lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs. J Neurosci 2007 27:6045-6053.
Zhao ZQ, Scott M, Chiechio S, Wang JS, Renner K, Gereau RW, Johnson R, Deneris E and Chen ZF. Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity. J Neurosci 2006 26:12781-12788.
Last Updated: 08/12/2009 |