{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:17:11Z","timestamp":1792016231699,"version":"4.4.0"},"reference-count":66,"publisher":"Society for Neuroscience","issue":"19","license":[{"start":{"date-parts":[[2012,11,9]],"date-time":"2012-11-09T00:00:00Z","timestamp":1352419200000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2012,5,9]]},"abstract":"<jats:p>\n                    A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using\n                    <jats:italic>in vivo<\/jats:italic>\n                    functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6\/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [\n                    <jats:sup>14<\/jats:sup>\n                    C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6\/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6\/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as\n                    <jats:italic>in vivo<\/jats:italic>\n                    biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0388-12.2012","type":"journal-article","created":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T13:01:26Z","timestamp":1336568486000},"page":"6456-6467","source":"Crossref","is-referenced-by-count":78,"title":["R6\/2 Huntington's Disease Mice Develop Early and Progressive Abnormal Brain Metabolism and Seizures"],"prefix":"10.1523","volume":"32","author":[{"given":"Efrain","family":"Cepeda-Prado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Popp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitre","family":"Stefanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana B.","family":"Menalled","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Dow-Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Small","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2012,5,9]]},"reference":[{"key":"2023041303561963000_32.19.6456.1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.6.2085"},{"key":"2023041303561963000_32.19.6456.2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200110000-00001"},{"key":"2023041303561963000_32.19.6456.3","doi-asserted-by":"publisher","DOI":"10.1159\/000023286"},{"key":"2023041303561963000_32.19.6456.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.043"},{"key":"2023041303561963000_32.19.6456.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2008.04.001"},{"key":"2023041303561963000_32.19.6456.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3141-06.2007"},{"key":"2023041303561963000_32.19.6456.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)06095-X"},{"key":"2023041303561963000_32.19.6456.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1592-09.2009"},{"key":"2023041303561963000_32.19.6456.9","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf226"},{"key":"2023041303561963000_32.19.6456.10","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.8.1066"},{"key":"2023041303561963000_32.19.6456.11","first-page":"1763","article-title":"Functional MR in the evaluation of dementia: correlation of abnormal dynamic cerebral blood volume measurements with changes in cerebral metabolism on positron emission tomography with fludeoxyglucose F 18","volume":"16","author":"Gonz\u00e1lez","year":"1995","journal-title":"AJNR Am J Neuroradiol"},{"key":"2023041303561963000_32.19.6456.12","doi-asserted-by":"publisher","DOI":"10.1038\/306234a0"},{"key":"2023041303561963000_32.19.6456.13","doi-asserted-by":"crossref","unstructured":"Huppert TJ Jones PB Devor A Dunn AK Teng IC Dale AM Boas DA (2009) Sensitivity of neural-hemodynamic coupling to alterations in cerebral blood flow during hypercapnia. J Biomed Opt 14:044038.","DOI":"10.1117\/1.3210779"},{"key":"2023041303561963000_32.19.6456.14","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.10091402"},{"key":"2023041303561963000_32.19.6456.15","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh047"},{"key":"2023041303561963000_32.19.6456.16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5698-08.2009"},{"key":"2023041303561963000_32.19.6456.17","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1589"},{"key":"2023041303561963000_32.19.6456.18","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199812000-00026"},{"key":"2023041303561963000_32.19.6456.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.08.033"},{"key":"2023041303561963000_32.19.6456.20","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61737-992-5_17"},{"key":"2023041303561963000_32.19.6456.21","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.2.3.447"},{"key":"2023041303561963000_32.19.6456.22","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2586(199901)9:1<44::AID-JMRI6>3.0.CO;2-7"},{"key":"2023041303561963000_32.19.6456.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2004.10.018"},{"key":"2023041303561963000_32.19.6456.24","doi-asserted-by":"publisher","DOI":"10.1038\/35084005"},{"key":"2023041303561963000_32.19.6456.25","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1523\/JNEUROSCI.17-14-05509.1997","article-title":"GABAergic neurons in barrel cortex show strong, whisker-dependent metabolic activation during normal behavior","volume":"17","author":"McCasland","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303561963000_32.19.6456.26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009793"},{"key":"2023041303561963000_32.19.6456.27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45691"},{"key":"2023041303561963000_32.19.6456.28","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1022"},{"key":"2023041303561963000_32.19.6456.29","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.10.1467"},{"key":"2023041303561963000_32.19.6456.30","doi-asserted-by":"crossref","unstructured":"Moreno H Burghardt NS Vela-Duarte D Masciotti J Hua F Fenton AA Schwaller B Small SA (2011) The absence of the calcium-buffering protein calbindin is associated with faster age-related decline in hippocampal metabolism. Hippocampus, Advance online publication. Retrieved March 29, 2012. doi:10.1002\/hipo.20957 .","DOI":"10.1002\/hipo.20957"},{"key":"2023041303561963000_32.19.6456.31","doi-asserted-by":"crossref","first-page":"8231","DOI":"10.1523\/JNEUROSCI.23-23-08231.2003","article-title":"Age-dependent impairment of somatosensory response in the amyloid precursor protein 23 transgenic mouse model of Alzheimer's disease","volume":"23","author":"Mueggler","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303561963000_32.19.6456.32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb01499.x"},{"key":"2023041303561963000_32.19.6456.33","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1097\/01.WCB.0000128533.84196.D8","article-title":"Selective uptake of [14C]2-deoxyglucose by neurons and astrocytes: high-resolution microautoradiographic imaging by cellular 14C-trajectography combined with immunohistochemistry","volume":"24","author":"Nehlig","year":"2004","journal-title":"J Cereb Blood Flow Metab"},{"key":"2023041303561963000_32.19.6456.34","unstructured":"Paxinos G Franklin KBJ (2001) The mouse brain in stereotaxic coordinates (Academic, San Diego), Ed 2."},{"key":"2023041303561963000_32.19.6456.35","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.73"},{"key":"2023041303561963000_32.19.6456.36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609833104"},{"key":"2023041303561963000_32.19.6456.37","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(72)90177-0"},{"key":"2023041303561963000_32.19.6456.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120178897"},{"key":"2023041303561963000_32.19.6456.39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341202"},{"key":"2023041303561963000_32.19.6456.40","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000065888.88988.6E"},{"key":"2023041303561963000_32.19.6456.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.09.043"},{"key":"2023041303561963000_32.19.6456.42","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.65.092101.142131"},{"key":"2023041303561963000_32.19.6456.43","first-page":"565","article-title":"Asymmetric image-template registration","volume":"12","author":"Sabuncu","year":"2009","journal-title":"Med Image Comput Comput Assist Interv"},{"key":"2023041303561963000_32.19.6456.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.09.017"},{"key":"2023041303561963000_32.19.6456.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.09.016"},{"key":"2023041303561963000_32.19.6456.46","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200508072"},{"key":"2023041303561963000_32.19.6456.47","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2586(200009)12:3<411::AID-JMRI6>3.0.CO;2-5"},{"key":"2023041303561963000_32.19.6456.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090106797"},{"key":"2023041303561963000_32.19.6456.49","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0029(20001001)51:1<101::AID-JEMT11>3.0.CO;2-H"},{"key":"2023041303561963000_32.19.6456.50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1977.tb10649.x"},{"key":"2023041303561963000_32.19.6456.51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006735107"},{"key":"2023041303561963000_32.19.6456.52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04323.x"},{"key":"2023041303561963000_32.19.6456.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2005.05.018"},{"key":"2023041303561963000_32.19.6456.54","doi-asserted-by":"publisher","DOI":"10.1038\/nm0298-159"},{"key":"2023041303561963000_32.19.6456.55","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/55\/18\/012"},{"key":"2023041303561963000_32.19.6456.56","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"2023041303561963000_32.19.6456.57","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198511000-00003"},{"key":"2023041303561963000_32.19.6456.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.01.010"},{"key":"2023041303561963000_32.19.6456.59","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/mrm.1910310605","article-title":"Microscopic susceptibility variation and transverse relaxation: theory and experiment","volume":"31","author":"Weisskoff","year":"1994","journal-title":"Magn Reson Med"},{"key":"2023041303561963000_32.19.6456.60","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10425"},{"key":"2023041303561963000_32.19.6456.61","doi-asserted-by":"publisher","DOI":"10.2174\/156720506779025161"},{"key":"2023041303561963000_32.19.6456.62","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2004.00087.x"},{"key":"2023041303561963000_32.19.6456.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2005.02.013"},{"key":"2023041303561963000_32.19.6456.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.015"},{"key":"2023041303561963000_32.19.6456.65","doi-asserted-by":"publisher","DOI":"10.1159\/000321681"},{"key":"2023041303561963000_32.19.6456.66","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1017\/S1355617707071214","article-title":"fMRI detection of early neural dysfunction in preclinical Huntington's disease","volume":"13","author":"Zimbelman","year":"2007","journal-title":"J Int Neuropsychol Soc"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0388-12.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T17:05:09Z","timestamp":1681405509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0388-12.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,9]]},"references-count":66,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2012,5,9]]},"published-print":{"date-parts":[[2012,5,9]]}},"alternative-id":["10.1523\/JNEUROSCI.0388-12.2012"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0388-12.2012","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,9]]}}}