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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)

 
153
Projects
USD 39.9 M
Aggregated funding amount
USD 261 K
Average funding amount
Project list item
MECHANISMS OF OPIOID RESISTANCE AFTER SPINAL CORD INJURY

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

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Neural Progenitor Cells for Mitigating Pain after Spinal Cord Injury

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

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A Placental Stem Cell Derived Treatment for Acquired Spinal Cord Injury

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USD 300,000
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Craig H Neilsen Foundation to Armin Blesch, Zhiyong Tan, Fletcher White

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Recovery of bladder function after SCI with opsin-based sensorimotor modulation

Craig H Neilsen Foundation to Jennifer DeBerry, Candace Floyd, Cary DeWitte

USD 299,683
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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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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
Myelotomy with Hemorrhagic Necrosis Removal in a Porcine SCI Model

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

USD 600,000
2018 - 2021
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Restoring motor axon circuits after spinal cord injury

Craig H Neilsen Foundation to Martin Oudega

USD 300,000
2017 - 2019
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Novel pharmacological treatment of acute spinal cord injury

Craig H Neilsen Foundation to Mark Noble, Chris Proschel, Philip J Horner

USD 600,000
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Regeneration of respiratory neural circuitry following SCI

Craig H Neilsen Foundation to Angelo C Lepore, Michael Aron Lane, George Smith, Angelo C Lepore

USD 300,000
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Optogenetic integration of grafted neural stem cells

Craig H Neilsen Foundation to Philip J Horner, Chet Moritz, Wei-Chuan Shih

USD 299,955
2017 - 2019
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Post-SCI Bladder Reflex Conditioning with Pelvic Neuromodulation

Craig H Neilsen Foundation to Zachary Danziger, Jacob Graves McPherson

USD 287,965
2017 - 2019
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Movement Asymmetries following Spinal Cord Injury

Craig H Neilsen Foundation to Yuming Lei

USD 150,000
2017 - 2019
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Combinatorial Therapies to Treat Breathing Impairments After Cervical SCI

Craig H Neilsen Foundation to Elisa Gonzalez-Rothi, Gordon Mitchell, Elisa Gonzalez-Rothi

USD 299,826
2017 - 2019
Project list item
Strength training to reduce nociceptor plasticity in SCI-induced pain

Craig H Neilsen Foundation to Megan Ryan Detloff

USD 300,000
2017 - 2019
Project list item
Training of Activity of Muscles Below the Injury Level in Complete SCI for Neuroprosthetic Control

Craig H Neilsen Foundation to Hunter Peckham, Kevin L Kilgore, Michael J Fu, Elizabeth Heald, Anne M Bryden, Ronald L. Hart, Betty Dunger

USD 586,208
2017 - 2020
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