Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET
Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuron...
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| creator | Reid, William C Casas, Rafael Papadakis, Georgios Z Muthusamy, Siva Lee, Dianne E Ibrahim, Wael G Nair, Anand Koziol, Deloris Maric, Dragan Hammoud, Dima A |
| description | Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era. |
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We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0152265</identifier><identifier>PMID: 27010205</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abnormalities ; Acquired immune deficiency syndrome ; Age ; AIDS ; Animal cognition ; Animals ; Autoradiography ; Behavior ; Behavior, Animal ; Biology and Life Sciences ; Biomarkers ; Brain research ; Cell death ; Cognition ; Cognitive ability ; Dementia ; Emission analysis ; Emotional behavior ; Exploratory behavior ; Fluorodeoxyglucose F18 ; Glucose ; Habituation ; Habituation (learning) ; HIV ; HIV-1 - genetics ; Human immunodeficiency virus ; Hypometabolism ; In vivo methods and tests ; Infectious diseases ; Male ; Medical imaging ; Medicine and Health Sciences ; Motor skill learning ; Motor task performance ; Neurodegeneration ; Neurons - metabolism ; Neurosciences ; Nuclear medicine ; Positron emission ; Positron emission tomography ; Rats ; Rats, Transgenic ; Research and Analysis Methods ; Rodents ; Tomography ; Toxicology</subject><ispartof>PloS one, 2016, Vol.11 (3), p.e0152265-e0152265</ispartof><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3715-23640b3b03585c5e09b0f095322967423d379a3c8de6e820baf88c76ffee39fc3</citedby><cites>FETCH-LOGICAL-c3715-23640b3b03585c5e09b0f095322967423d379a3c8de6e820baf88c76ffee39fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807106/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807106/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,4010,23845,27900,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27010205$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zheng, Jialin Charles</contributor><creatorcontrib>Reid, William C</creatorcontrib><creatorcontrib>Casas, Rafael</creatorcontrib><creatorcontrib>Papadakis, Georgios Z</creatorcontrib><creatorcontrib>Muthusamy, Siva</creatorcontrib><creatorcontrib>Lee, Dianne E</creatorcontrib><creatorcontrib>Ibrahim, Wael G</creatorcontrib><creatorcontrib>Nair, Anand</creatorcontrib><creatorcontrib>Koziol, Deloris</creatorcontrib><creatorcontrib>Maric, Dragan</creatorcontrib><creatorcontrib>Hammoud, Dima A</creatorcontrib><title>Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era.</description><subject>Abnormalities</subject><subject>Acquired immune deficiency syndrome</subject><subject>Age</subject><subject>AIDS</subject><subject>Animal cognition</subject><subject>Animals</subject><subject>Autoradiography</subject><subject>Behavior</subject><subject>Behavior, Animal</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Brain research</subject><subject>Cell death</subject><subject>Cognition</subject><subject>Cognitive ability</subject><subject>Dementia</subject><subject>Emission analysis</subject><subject>Emotional behavior</subject><subject>Exploratory behavior</subject><subject>Fluorodeoxyglucose F18</subject><subject>Glucose</subject><subject>Habituation</subject><subject>Habituation (learning)</subject><subject>HIV</subject><subject>HIV-1 - 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We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27010205</pmid><doi>10.1371/journal.pone.0152265</doi><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abnormalities Acquired immune deficiency syndrome Age AIDS Animal cognition Animals Autoradiography Behavior Behavior, Animal Biology and Life Sciences Biomarkers Brain research Cell death Cognition Cognitive ability Dementia Emission analysis Emotional behavior Exploratory behavior Fluorodeoxyglucose F18 Glucose Habituation Habituation (learning) HIV HIV-1 - genetics Human immunodeficiency virus Hypometabolism In vivo methods and tests Infectious diseases Male Medical imaging Medicine and Health Sciences Motor skill learning Motor task performance Neurodegeneration Neurons - metabolism Neurosciences Nuclear medicine Positron emission Positron emission tomography Rats Rats, Transgenic Research and Analysis Methods Rodents Tomography Toxicology |
| title | Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T17%3A55%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neurobehavioral%20Abnormalities%20in%20the%20HIV-1%20Transgenic%20Rat%20Do%20Not%20Correspond%20to%20Neuronal%20Hypometabolism%20on%2018F-FDG-PET&rft.jtitle=PloS%20one&rft.au=Reid,%20William%20C&rft.date=2016&rft.volume=11&rft.issue=3&rft.spage=e0152265&rft.epage=e0152265&rft.pages=e0152265-e0152265&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0152265&rft_dat=%3Cproquest_plos_%3E3997134451%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1775626268&rft_id=info:pmid/27010205&rft_doaj_id=oai_doaj_org_article_d0c6c35a5e434ea7af731ae1c6cfd5ab&rfr_iscdi=true |