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Cypin inhibition as an approach to treat spinal cord injury-induced neuropathic pain
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Singh, Nisha K.. Cypin inhibition as an approach to treat spinal cord injury-induced neuropathic pain. Retrieved from https://doi.org/doi:10.7282/t3-p74s-8k04

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TitleCypin inhibition as an approach to treat spinal cord injury-induced neuropathic pain
NameSingh, Nisha K. (author); Firestein, Bonnie (chair); Elkabes, Stella (member); Zhou, Renping (member); Cai, Li (member); Pang, Zhiping (member); Rutgers University; School of Graduate Studies
Date Created2022
Other Date2022-10 (degree)
SubjectCellular biology, Developmental biology, Cypin, Guanine deaminase, Neuropathic pain, Spinal cord injury
DescriptionSpinal cord injury (SCI) involves a primary mechanical phase of injury that results in physical damage to spinal cord tissue and a secondary phase characterized by alterations in molecular signaling that exacerbate the effects of tissue damage. Dysregulation of these cellular processes during the secondary phase of SCI contributes to a host of pathologies including neuroinflammation, loss of motor and autonomic function, and neuropathic pain. Better characterization of the mechanisms underlying secondary injury is crucial for the development of novel targeted therapeutics. Glutamate-induced excitotoxicity is a key contributor to secondary injury, but the signaling pathways that are activated downstream are not completely understood. Modulation of purine metabolism represents a promising approach to mitigating some of the harmful effects of GIE. Guanine-based purines (GBPs), such as guanosine, have been shown to confer neuroprotection and reduce neuropathic pain after SCI, although the mechanisms of action remain largely unknown. In this project, we investigate the potential role of guanine metabolism in recovery after SCI. The guanine deaminase (GDA) enzyme, cypin, catalyzes metabolism of guanine to xanthine and regulates dendrite morphology. We utilize an in vitro model of glutamate-induced excitotoxicity (GIE) in primary spinal cord cultures and an in vivo model of contusion SCI in mice to evaluate the effects of cypin modulation on recovery from SCI. We implemented a combination of immunohistochemical, Western blot, and behavioral analyses for these assessments. Our data suggest that inhibition of cypin GDA activity has both neuroprotective and pain-alleviating effects. We demonstrate that cypin inhibitors preserve neuronal viability after GIE, alleviate mechanical pain sensitivity in injured mice, and lead to an upregulation of A2A adenosine receptors (A2AARs) in the lumbar dorsal horn (LDH) of the spinal cord after SCI. This research examines the pain-attenuating effects of cypin inhibition after SCI and explores modulation of purinergic signaling as a possible mechanism by which these effects are exerted.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
Persistent URLhttps://doi.org/doi:10.7282/t3-p74s-8k04
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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