{"654081":{"#nid":"654081","#data":{"type":"news","title":"Tangled Messages: Tracing Neural Circuits to Chemotherapy\u0027s \u0027Constellation of Side Effects\u0027 ","body":[{"value":"\u003Cp\u003ESevere and persistent disability often undermines the life-saving benefits of cancer treatment. Pain and fatigue \u0026mdash; together with sensory, motor, and cognitive disorders \u0026mdash; are chief among the constellation of side effects that occur with the platinum-based agents used widely in chemotherapy treatments worldwide.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EA new study by Georgia Tech researchers in the lab of \u003Ca href=\u0022https:\/\/biosciences.gatech.edu\/people\/timothy-cope\u0022\u003ETimothy C. Cope\u003C\/a\u003E has found a novel pathway for understanding why these debilitating conditions happen for cancer patients and why scientists should focus on all of the possible neural processes that deliver sensory or motor problems to a patient\u0026rsquo;s brain \u0026mdash; including the central nervous system \u0026mdash; and not just the \u0026ldquo;peripheral degeneration of sensory neurons\u0026rdquo; that occurs away from the center of the body.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe new findings \u003Ca href=\u0022https:\/\/www.pnas.org\/content\/118\/51\/e2100428118\u0022\u003E\u0026ldquo;Neural circuit mechanisms of sensorimotor disability in cancer treatment\u0026rdquo;\u003C\/a\u003E are published in the \u003Ca href=\u0022https:\/\/www.pnas.org\/\u0022\u003EProceedings of the National Academy of Sciences (PNAS)\u003C\/a\u003E and could impact development of effective treatments that are not yet available for restoring a patient\u0026rsquo;s normal abilities to receive and process sensory input as part of post cancer treatment, in particular.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Ca href=\u0022https:\/\/www.researchgate.net\/profile\/Stephen-Housley\u0022\u003EStephen N. (Nick) Housley\u003C\/a\u003E, a postdoctoral researcher in the \u003Ca href=\u0022https:\/\/biosciences.gatech.edu\/\u0022\u003ESchool of Biological Sciences\u003C\/a\u003E, the \u003Ca href=\u0022https:\/\/research.gatech.edu\/john-mcdonald\u0022\u003EIntegrated Cancer Research Center\u003C\/a\u003E, and the \u003Ca href=\u0022https:\/\/research.gatech.edu\/bio\u0022\u003EParker H. Petit Institute for Bioengineering and Bioscience\u003C\/a\u003E at Georgia Tech, is the study\u0026rsquo;s lead author. Co-authors include \u003Ca href=\u0022https:\/\/biosciences.gatech.edu\/people\/paul-nardelli\u0022\u003EPaul Nardelli\u003C\/a\u003E, research scientist and \u003Ca href=\u0022https:\/\/sites.gatech.edu\/copelab\/http-pwp-gatech-edu-copelab-http-pwp-gatech-edu-copelab-people-paul-nardelli-paul-nardelli\/travis-rotterman-ph-d\/\u0022\u003ETravis Rotterman\u003C\/a\u003E, postdoctoral fellow (both of the School of Biological Sciences), along with \u003Ca href=\u0022https:\/\/biosciences.gatech.edu\/people\/timothy-cope\u0022\u003ETimothy Cope\u003C\/a\u003E, who serves as a professor with joint appointments in the School of Biological Sciences at Georgia Tech and in the \u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/\u0022\u003ECoulter Department of Biomedical Engineering\u003C\/a\u003E at Emory University and Georgia Tech.\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003ENeurologic consequences\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;Chemotherapy undoubtedly negatively influences the peripheral nervous system, which is often viewed as the main culprit of neurologic disorders during cancer treatment,\u0026rdquo; shares Housley. However, he says, for the nervous system to operate normally, both the peripheral and central nervous system must cooperate.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;This occurs through synaptic communication between neurons. Through an elegant series of studies, we show that those hubs of communication in the central nervous system are also vulnerable to cancer treatment\u0026rsquo;s adverse effects,\u0026rdquo; Housley shares, adding that the findings force \u0026ldquo;recognition of the numerous places throughout the nervous system that we have to treat if we ever want to fix the neurological consequences of cancer treatment \u0026mdash; because correcting any one may not be enough to improve human function and quality of life.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;These disabilities remain clinically unmitigated and empirically unexplained as research concentrates on peripheral degeneration of sensory neurons,\u0026rdquo; the research team explains in the study, \u0026ldquo;while understating the possible involvement of neural processes within the central nervous system. The present findings demonstrate functional defects in the fundamental properties of information processing localized within the central nervous system,\u0026rdquo; concluding that \u0026ldquo;long-lasting sensorimotor and possibly other disabilities induced by cancer treatment result from independent neural defects compounded across both peripheral and central nervous systems.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003ESensorimotor disabilities and \u0026lsquo;cOIN\u0026rsquo;\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003EThe research team notes that cancer survivors \u0026ldquo;rank sensorimotor disability among the most distressing, long-term consequences of chemotherapy. Disorders in gait, balance, and skilled movements are commonly assigned to chemotoxic damage of peripheral sensory neurons without consideration of the deterministic role played by the neural circuits that translate sensory information into movement,\u0026rdquo; adding that this oversight \u0026ldquo;precludes sufficient, mechanistic understanding and contributes to the absence of effective treatment for reversing chemotherapy-induced disability.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003ECope says the team resolved this omission \u0026ldquo;through the use of a combination of electrophysiology, behavior, and modeling to study the operation of a spinal sensorimotor circuit in\u0026nbsp;vivo\u0026rdquo; in a rodent model of \u0026ldquo;chronic, oxaliplatin (chemotherapy)\u0026ndash;induced neuropathy: cOIN.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EKey sequential events were studied in the encoding of \u0026ldquo;propriosensory\u0026rdquo; information (think kinesthesia: the body\u0026#39;s ability to sense its location, movements, and actions) and its circuit translation into the synaptic potentials produced in motoneurons.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn the \u0026ldquo;cOIN\u0026rdquo; rats, the team noted multiple classes of propriosensory neurons expressed defective firing that reduced accurate sensory representation of muscle mechanical responses to stretch, adding that accuracy \u0026ldquo;degraded further in the translation of propriosensory signals into synaptic potentials as a result of defective mechanisms residing inside the spinal cord.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Ch4\u003E\u003Cstrong\u003EJoint expression, independent defects\u003C\/strong\u003E\u003C\/h4\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;These sequential, peripheral, and central defects compounded to drive the sensorimotor circuit into a functional collapse that was consequential in predicting the significant errors in propriosensory-guided movement behaviors demonstrated here in our rat model and reported for people with cOIN,\u0026rdquo; Cope and Housley report. \u0026ldquo;We conclude that sensorimotor disability induced by cancer treatment emerges from the joint expression of independent defects occurring in both peripheral and central elements of sensorimotor circuits.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;These findings have broad impact on the scientific field and on clinical management of neurologic consequences of cancer treatment,\u0026rdquo; Housley says. \u0026ldquo;As both a clinician and scientist, I can envision the urgent need to jointly develop quantitative clinical tests that have the capacity to identify which parts of a patient nervous system are impacted by their cancer treatment.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EHousley also says that having the capacity to monitor neural function across various sites during the course of treatment \u0026ldquo;will provide a biomarker on which we can optimize treatment \u0026mdash; e.g. maximize anti-neoplastic effects while minimizing the adverse effects,\u0026rdquo; adding that, as we move into the next generation cancer treatments, \u0026ldquo;clinical tests that can objectively monitor specific aspects of the nervous system will be exceptionally important to test for the presence off-target effect.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003E***\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EFUNDING: \u003C\/strong\u003EThis work is supported by NIH Grants R01CA221363 and R01HD090642 and the Northside Hospital Foundation, Inc.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EDOI: \u003C\/strong\u003Edoi.org\/10.1073\/pnas.2100428118\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EACKNOWLEDGMENTS: \u003C\/strong\u003EThe researchers thank Marc Binder (Department of Physiology \u0026amp; Biophysics at University of Washington) and Todd Streelman (School of Biological Sciences at Georgia Tech) for providing useful discussions and comments on a preliminary version of the manuscript. Lead author Housley also serves as chief scientific officer for Motus Nova, a healthcare robotics and technology company.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003E***\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe Georgia Institute of Technology, or Georgia Tech, is a top 10 public research university developing leaders who advance technology and improve the human condition. The Institute offers business, computing, design, engineering, liberal arts, and sciences degrees. Its nearly 44,000 students representing 50 states and 149 countries, study at the main campus in Atlanta, at campuses in France and China, and through distance and online learning. As a leading technological university, Georgia Tech is an engine of economic development for Georgia, the Southeast, and the nation, conducting more than $1 billion in research annually for government, industry, and society.\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Tim Cope and Nick Housley unravel the neural pathways behind complex sensory and motor side effects of chemotherapy"}],"field_summary":[{"value":"\u003Cp\u003ECancer patients undergoing chemotherapy can experience severe side effects that persist long after treatments end. A new study led by Tim Cope and Nick Housley has found a novel pathway for understanding why these debilitating conditions happen \u0026mdash; and why scientists should focus on \u0026quot;all of the possible neural processes that deliver sensory or motor problems to a patient\u0026rsquo;s brain\u0026quot; and not just those that occur away from the center of the body.\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"Tim Cope and Nick Housley unravel the neural pathways behind complex sensory and motor side effects of chemotherapy, share why scientists should focus on \u0022all of the possible neural processes that deliver sensory or motor problems to a patient\u2019s brain\u0022"}],"uid":"34528","created_gmt":"2022-01-05 17:55:25","changed_gmt":"2022-01-07 17:19:26","author":"jhunt7","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2022-01-06T00:00:00-05:00","iso_date":"2022-01-06T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"654082":{"id":"654082","type":"image","title":"Cancer survivors rank disorders in gait, balance, and skilled movements among the most distressing, long-term consequences of chemotherapy. (Photo: CDC)","body":null,"created":"1641405485","gmt_created":"2022-01-05 17:58:05","changed":"1641405485","gmt_changed":"2022-01-05 17:58:05","alt":"","file":{"fid":"248091","name":"man-in-wheelchair-wearing-mask.jpg","image_path":"\/sites\/default\/files\/images\/man-in-wheelchair-wearing-mask.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/man-in-wheelchair-wearing-mask.jpg","mime":"image\/jpeg","size":61279,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/man-in-wheelchair-wearing-mask.jpg?itok=mpGaElYE"}},"654083":{"id":"654083","type":"image","title":"Study shows certain disabilities induced by cancer treatments emerge from the joint expression of independent defects across peripheral and central sensorimotor circuits. (Photo: CDC)","body":null,"created":"1641405862","gmt_created":"2022-01-05 18:04:22","changed":"1641405862","gmt_changed":"2022-01-05 18:04:22","alt":"","file":{"fid":"248092","name":"chemo-700sq.jpg","image_path":"\/sites\/default\/files\/images\/chemo-700sq.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/chemo-700sq.jpg","mime":"image\/jpeg","size":25210,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/chemo-700sq.jpg?itok=L4lMHgiI"}},"654084":{"id":"654084","type":"image","title":"With new research published in PNAS, researchers show that \u0022hubs of communication in the central nervous system are also vulnerable to cancer treatment\u2019s adverse effects.\u0022 (Graphic of neuron firing: NIH)","body":null,"created":"1641406046","gmt_created":"2022-01-05 18:07:26","changed":"1641406046","gmt_changed":"2022-01-05 18:07:26","alt":"","file":{"fid":"248093","name":"neuron firing.jpg","image_path":"\/sites\/default\/files\/images\/neuron%20firing.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/neuron%20firing.jpg","mime":"image\/jpeg","size":97182,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/neuron%20firing.jpg?itok=hhSn31nW"}},"593191":{"id":"593191","type":"image","title":"Tim Cope","body":null,"created":"1498853589","gmt_created":"2017-06-30 20:13:09","changed":"1498853589","gmt_changed":"2017-06-30 20:13:09","alt":"","file":{"fid":"226107","name":"Sidebar.TimCope.jpg","image_path":"\/sites\/default\/files\/images\/Sidebar.TimCope.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/Sidebar.TimCope.jpg","mime":"image\/jpeg","size":239961,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/Sidebar.TimCope.jpg?itok=XRf4KtFL"}},"654085":{"id":"654085","type":"image","title":"Nick Housley","body":null,"created":"1641406366","gmt_created":"2022-01-05 18:12:46","changed":"1641406366","gmt_changed":"2022-01-05 18:12:46","alt":"","file":{"fid":"248094","name":"1*oo7GziHZPlAm3h-ftulYDA.jpeg","image_path":"\/sites\/default\/files\/images\/1%2Aoo7GziHZPlAm3h-ftulYDA.jpeg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/1%2Aoo7GziHZPlAm3h-ftulYDA.jpeg","mime":"image\/jpeg","size":330393,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/1%2Aoo7GziHZPlAm3h-ftulYDA.jpeg?itok=IvTXC6x9"}}},"media_ids":["654082","654083","654084","593191","654085"],"related_links":[{"url":"https:\/\/research.gatech.edu\/chemotherapy-and-cancer-gang-cause-neurological-side-effect-study-says","title":"Chemotherapy and Cancer Gang up to Cause a Neurological Side Effect, Study Says "},{"url":"https:\/\/research.gatech.edu\/multi-algorithm-approach-helps-deliver-personalized-medicine-cancer-patients","title":"Multi-Algorithm Approach Helps Deliver Personalized Medicine for Cancer Patients "},{"url":"https:\/\/research.gatech.edu\/petit-institute-seed-grants-awarded-three-teams","title":"Petit Institute Seed Grants Awarded to Three Teams "}],"groups":[{"id":"1278","name":"College of Sciences"},{"id":"1188","name":"Research Horizons"},{"id":"1275","name":"School of Biological Sciences"}],"categories":[{"id":"135","name":"Research"},{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"},{"id":"140","name":"Cancer Research"},{"id":"146","name":"Life Sciences and Biology"}],"keywords":[{"id":"166882","name":"School of Biological Sciences"},{"id":"187915","name":"go-researchnews"},{"id":"187423","name":"go-bio"},{"id":"189637","name":"Nick Housley"},{"id":"174814","name":"Tim Cope"},{"id":"189638","name":"Paul Nardelli"},{"id":"189639","name":"Travis Rotterman"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"},{"id":"39501","name":"People and Technology"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Cstrong\u003EWriter:\u003C\/strong\u003E\u003Cbr \/\u003E\r\nRenay San Miguel\u003Cbr \/\u003E\r\nCommunications Officer II\/Science Writer\u003Cbr \/\u003E\r\nCollege of Sciences\u003Cbr \/\u003E\r\n404-894-5209\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EEditor and Media Contact: \u003C\/strong\u003E\u003Cbr \/\u003E\r\n\u003Ca href=\u0022mailto:jess@cos.gatech.edu\u0022\u003EJess Hunt-Ralston\u003C\/a\u003E\u003Cbr \/\u003E\r\nDirector of Communications\u003Cbr \/\u003E\r\nCollege of Sciences\u003C\/p\u003E\r\n","format":"limited_html"}],"email":["jess@cos.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}