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Project

Determining spinal alterations in sexual reflex control.

Funder: Craig H Neilsen Foundation

Funding period
USD 600 K
Funding amount
Abstract
Spinal cord injury (SCI) has detrimental effects on a wide variety of functions and systems. Of particular relevance to this proposal, recovery of sexual function is rated as a high priority among paraplegic men. SCI in men is commonly associated with ejaculatory dysfunction. However, there are no effective non-invasive treatments for anejaculation in SCI men. The overall goal of our research is therefore to further our understanding of the mechanisms by which SCI impacts the neural mechanisms controlling ejaculation, thereby enhancing advancements in restoration of fertility and sexual dysfunction in chronic SCI patients.Ejaculation is a spinal reflex that requires an integration of sensory inputs and coordinated output of sympathetic, parasympathetic and motor neurons located in the lumbosacral spinal cord. This integration is controlled by the spinal ejaculation generator (SEG). Previously, our lab identified the population of neurons that comprise the SEG in male rats, consisting of lumbar spinothalamic cells (LSt cells) located in lumbar spinal levels L3-4. LSt cells have axonal projections to the autonomic and motor neurons necessary for ejaculation, located in upper lumbar and sacral spinal levels. LSt cells and axons co-contain the neuropeptides enkephalin, galanin, cholecystokinin and gastrin releasing peptide. Release of these neuropeptides from LSt axons to autonomic and motor nuclei is essential for ejaculation, as infusions of receptor antagonists prevent ejaculation. Moreover, we have demonstrated that infusions of receptor agonists can trigger or facilitate ejaculation and can thus be potential targets for treatment of ejaculatory dysfunction. The SEG has recently been confirmed to be identical in its anatomical location and neuropeptide expression in human males, allowing for optimal translation of findings in rat models to neural control of ejaculatory function in humans.Furthermore, we recently demonstrated that SCI disrupts ejaculation in male rats, comparable to the anejaculation in men with chronic SCI. Contusion injury at mid thoracic level in male rats caused long-term anejaculation, due to neural alterations in the SEG. Hence, our overall hypothesis is that the chronic injury to the spinal pathways at levels above the SEG result in long-term neural pathology within the spinal ejaculation generator, thereby causing ejaculatory dysfunction. In the current proposal, we will specifically test the hypothesis that chronic SCI impairs the synthesis of neuropeptides in LSt cells and the connections of LSt cells to autonomic and motor cells to release the neuropeptides required for ejaculatory reflexes. We will employ a multidisciplinary approach and integrate anatomical, molecular, and pharmacological techniques to test this hypothesis. Together, these studies will greatly advance our understanding of the neural plasticity by which chronic SCI impacts ejaculatory function and may identify new targets for future treatments. (CHN: SCIRTS chn:wdg)

 
159
Projects
USD 42.7 M
Aggregated funding amount
USD 268 K
Average funding amount
Project list item
The intraspinal serotonergic system regulates micturition reflexe after SCI

Craig H Neilsen Foundation to Yu-Shang Lee

USD 300,000
2019 - 2021
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Molecular control over motor circuit remodeling

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USD 300,000
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Biological light stimulation to restore function after SCI

Craig H Neilsen Foundation to Ute Hochgeschwender, Griffin E. Kendziorski, Ute Hochgeschwender, Eric D. Petersen

USD 300,000
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Cervical Spinal Epidural Stimulation and Respiratory Recovery After SCI

Craig H Neilsen Foundation to Erica Dale, Erica Dale

USD 300,000
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Novel chemical approaches for specific targeting of CSPGs to restore function after SCI

Craig H Neilsen Foundation to Linda Carol Hsieh-Wilson, Elizabeth Jane Bradbury

USD 600,000
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Role of ENaC in Spinal Cord Injury

Craig H Neilsen Foundation to Heping Ma, Shawn Hochman, Sandra Garraway

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Spinal Cord Stimulation for Restoration of Bladder Function

Craig H Neilsen Foundation to Warren M Grill

USD 300,000
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Transcutaneous spinal stimulation to improve hand function after SCI

Craig H Neilsen Foundation to Chet Moritz, Stephen P. Burns, Fatma Inanici, Soshi Samejima, Vicente Martinez, Christoph Hofstetter

USD 300,000
2019 - 2021
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Functional map of spinal cord stimulation

Craig H Neilsen Foundation to CJ Heckman

USD 600,000
2019 - 2022
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Neural Pathways and Recovery of Motor Function with Epidural Stimulation

Craig H Neilsen Foundation to Jessica Maria D'Amico, Claudia Angeli, Susan Harkema

USD 300,000
2019 - 2021
Project list item
Metabolic reprograming of glial cells promotes axon regeneration in the CNS

Craig H Neilsen Foundation to Yuanquan Song

USD 300,000
2019 - 2021
Project list item
Psychosocial, cognitive, and behavioral consequences of sleep-disordered breathing in SCI people

Craig H Neilsen Foundation to Julio Cesar Furlan, Mark I Boulos, Sander L Hitizg, B. Catharine Craven

USD 200,000
2019 - 2021
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Toll-like receptor 4 signaling in chronic neuropathic pain after SCI

Craig H Neilsen Foundation to Armin Blesch, Zhiyong Tan, Fletcher White

USD 300,000
2018 - 2020
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MECHANISMS OF OPIOID RESISTANCE AFTER SPINAL CORD INJURY

Craig H Neilsen Foundation to Carmen W Dessauer, Michelle Hook, Edgar Walters

USD 600,000
2018 - 2021
Project list item
Myelotomy with Hemorrhagic Necrosis Removal in a Porcine SCI Model

Craig H Neilsen Foundation to Maxwell Boakye, Beatrice Ugiliweneza, Brian K Kwon, Leslie Sherwood, Dena Howland, April Herrity, Charles Hubscher, Junqian Xu, Robert Bert

USD 600,000
2018 - 2021
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Neural Progenitor Cells for Mitigating Pain after Spinal Cord Injury

Craig H Neilsen Foundation to Jennifer N Dulin, James Grau, Jennifer N Dulin

USD 299,135
2018 - 2020
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Property of vasoconstrictor thoracic sympathetic postganglionic neurons after SCI

Craig H Neilsen Foundation to Yaqing Li

USD 150,000
2018 - 2020
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Effects of single-day AIH on rebalancing excitatory and inhibitory transmission in persons with iSCI

Craig H Neilsen Foundation to Andrew Tan, Randy Trumbower, Lorna Brown

USD 150,000
2018 - 2020
Project list item
Zinc chelation to promote axon regeneration after spinal cord injury

Craig H Neilsen Foundation to Sheri Lynn Peterson

USD 148,728
2018 - 2020
Project list item
Effects of spinal cord injury and locomotor training on colonic motility.

Craig H Neilsen Foundation to Robert Hoey

USD 150,000
2018 - 2020
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