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Welcome to the Xie Lab
Alison Xiaoqiao Xie, PhD
Research Interests
The Xie lab studies satellite glia-neuron interactions in the peripheral nervous system. Several populations of peripheral glia, including satellite glial cells in the peripheral ganglia and terminal glia in organs, can modulate afferent and efferent activity and targeted organ functions. We use mouse models in which the glial cell signaling can be manipulated in vivo to study the neuromodulatory functions of these glial cells.
Active Research Projects
The Role of Sensory Satellite Glia in Chronic Pelvic Pain
Patients with urological chronic pelvic pain syndrome (UCPPS) experience chronic pelvic pain (CPP) and lower urinary tract symptoms (LUTS). The UCPPS symptoms are closely associated with nociceptive sensitization in the nervous system, which underlies visceral allodynia and hyperalgesia. Previous studies suggested that afferent hypersensitivity in bladder-projecting sensory neurons plays an important role in the generation and the maintenance of UCPPS symptoms, especially bladder pain and urinary frequency. We have found that Gq-GPCR activation in satellite glial cells (SGCs) in the sensory ganglia decreases afferent sensitivity in lumbar nociceptive assays, a promising and highly innovative approach to alleviate the symptoms of bladder overactivity and pain. The current work focuses on 1) developing experimental approaches for targeted activation of Gq-GPCR signaling pathways in sensory SGCs; 2) assessing the changes in lumbosacral bladder afferent sensitivity following glial Gq-GPCR activation; and 3) evaluating the glial activation-induced changes in LUTS and visceral hypersensitivity in vivo and in mouse models of UCPPS. Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gq-DREADD) is used to selectively activate Gq-GPCR signaling cascades in lumbosacral sensory SGCs via targeted adeno-associated virus (AAV) delivery. Afferent sensitivity and bladder functions are evaluated in vivo by well-established and clinically-relevant visceral nociceptive assays and urodynamic assays. This project aims to characterize the role of SGC Gq-GPCR signaling in regulating visceral nociception in vivo as well as test its therapeutic potential to reverse pain and voiding dysfunction in UCPPS patients.
Sex Differences in Sympathetic Satellite Glial Regulation of Blood Pressure
This study aims to reveal the sexual dimorphism in sympathetic glial regulation of cardio output and blood pressure. Our preliminary data strongly suggest that Gq-GPCR activation in sympathetic ganglionic glia cells positively regulates postganglionic neuronal activity and sympathetic output, and in turn increases cardio output and resting blood pressure. However, prolonged glial-driven sympathoactivation induces hypotension, suggesting homeostatic plasticity in glial influences on sympathetic output/blood pressure. Interestingly, the hypotension phenotype was only observed in female animals. This project proposal is designed to reveal the sex differences in the pathogenesis chronic sympathoactivation induced cardiovascular dysfunction, as well as perform transcriptome profiling in the glia-neuron interactions in sympathetic ganglia. This study will lead to new discoveries in sex-specific mechanisms underlying sympathetic regulation of physiological cardiovascular functions and/or neurogenic hypertension.
Autonomic Satellite Glial Control of Micturition
The urinary bladder collects and stores urine before releasing it at behaviorally appropriate times. Proper bladder functions are controlled by autonomic nerve activity descending from the major pelvic ganglia. Current preparations lack the ability to perturb the signaling events in neurons or glia in the pelvic ganglia, limiting our ability to study the glia-neuron interactions within the pelvic ganglia and their impact on bladder functions. This proposal aims to develop a major pelvic ganglia-bladder preparation in which both neurons and glial cells in the pelvic ganglia can be optogenetically activated or silenced. Simultaneously, we will record whole bladder contractions as a readout for micturition function. The development of this ex vivo mouse preparation will enable future hypothesis testing of the neuromodulatory roles of autonomic glia and other non-neuronal cell types in bladder physiology, as well as the therapeutic potential of pharmacological agents on treating neurogenic bladder dysfunctions.