{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:53:19Z","timestamp":1780473199073,"version":"3.54.1"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Research"],"published-print":{"date-parts":[[2007,1]]},"DOI":"10.1016\/j.brainres.2006.09.101","type":"journal-article","created":{"date-parts":[[2006,11,16]],"date-time":"2006-11-16T19:15:43Z","timestamp":1163704543000},"page":"136-150","source":"Crossref","is-referenced-by-count":22,"special_numbering":"C","title":["PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pahenu2 mice"],"prefix":"10.1016","volume":"1127","author":[{"given":"Jennifer E.","family":"Embury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Charron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoly","family":"Martynyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas G.","family":"Zori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed F.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil E.","family":"Rowland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Laipis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.brainres.2006.09.101_bib1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0006-8993(09)90007-5","article-title":"Low environmental temperatures or pharmacologic agents that produce hypothermia decrease methamphetamine neurotoxicity in mice","volume":"658","author":"Ali","year":"1994","journal-title":"Brain Res."},{"key":"10.1016\/j.brainres.2006.09.101_bib2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1023\/A:1010500502275","article-title":"Plasma phenylalanine is associated with decreased serum ubiquinone-10 concentrations in phenylketonuria","volume":"24","author":"Artuch","year":"2001","journal-title":"J. Inherit. Metab Dis."},{"key":"10.1016\/j.brainres.2006.09.101_bib3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.clinbiochem.2003.10.017","article-title":"A longitudinal study of antioxidant status in phenylketonuric patients","volume":"37","author":"Artuch","year":"2004","journal-title":"Clin. Biochem."},{"key":"10.1016\/j.brainres.2006.09.101_bib4","doi-asserted-by":"crossref","first-page":"29409","DOI":"10.1016\/S0021-9258(18)43894-X","article-title":"Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide","volume":"269","author":"Castro","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.brainres.2006.09.101_bib5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1006\/abbi.1998.0898","article-title":"Nitric oxide and peroxynitrite-dependent aconitase inactivation and iron-regulatory protein-1 activation in mammalian fibroblasts","volume":"359","author":"Castro","year":"1998","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.brainres.2006.09.101_bib6","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.neuroscience.2004.04.020","article-title":"Identification of brain-derived neurotrophic factor in nestin-expressing astroglial cells in the neostriatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice","volume":"126","author":"Chen","year":"2004","journal-title":"Neuroscience"},{"key":"10.1016\/j.brainres.2006.09.101_bib7","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/sj.ejcn.1601631","article-title":"Plasma thiols and their determinants in phenylketonuria","volume":"57","author":"Colome","year":"2003","journal-title":"Eur. J. Clin. Nutr."},{"key":"10.1016\/j.brainres.2006.09.101_bib8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/BF00690534","article-title":"A study of cerebellar and cerebral cortical degeneration in miniature poodle pups with emphasis on the ultrastructure of Purkinje cell changes","volume":"75","author":"Cummings","year":"1988","journal-title":"Acta Neuropathol. (Berl)"},{"key":"10.1016\/j.brainres.2006.09.101_bib9","first-page":"1271","article-title":"Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis","volume":"145","author":"Dal Canto","year":"1994","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.brainres.2006.09.101_bib10","doi-asserted-by":"crossref","first-page":"i","DOI":"10.2307\/1166208","article-title":"Prefrontal cortex cognitive deficits in children treated early and continuously for PKU","volume":"62","author":"Diamond","year":"1997","journal-title":"Monogr. Soc. Res. Child Dev."},{"key":"10.1016\/j.brainres.2006.09.101_bib11","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/BF00965524","article-title":"Effects of phenylalanine and its deaminated metabolites on Na+, K+-ATPase activity in synaptosomes from rat brain","volume":"7","author":"Dwivedy","year":"1982","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.brainres.2006.09.101_bib12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1203\/01.PDR.0000170000.78670.44","article-title":"Pathologic and immunohistochemical findings in hypothalamic and mesencephalic regions in the pah(enu2) mouse model for phenylketonuria","volume":"58","author":"Embury","year":"2005","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.brainres.2006.09.101_bib13","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/S0891-5849(02)00781-5","article-title":"Oxidative stress in a phenylketonuria animal model","volume":"32","author":"Ercal","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.brainres.2006.09.101_bib14","series-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Franklin","year":"1997"},{"key":"10.1016\/j.brainres.2006.09.101_bib15","doi-asserted-by":"crossref","first-page":"685","DOI":"10.2165\/00002512-200118090-00004","article-title":"Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment","volume":"18","author":"Halliwell","year":"2001","journal-title":"Drugs Aging"},{"key":"10.1016\/j.brainres.2006.09.101_bib16","series-title":"Free Radicals in Biology and Medicine","author":"Halliwell","year":"1989"},{"key":"10.1016\/j.brainres.2006.09.101_bib17","series-title":"Free Radicals in Biology and Medicine","author":"Halliwell","year":"1989"},{"issue":"Suppl. 2","key":"10.1016\/j.brainres.2006.09.101_bib18","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1007\/PL00014371","article-title":"The neuropathology of phenylketonuria: human and animal studies","volume":"159","author":"Huttenlocher","year":"2000","journal-title":"Eur. J. Pediatr."},{"key":"10.1016\/j.brainres.2006.09.101_bib19","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1073\/pnas.96.6.3160","article-title":"A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients","volume":"96","author":"Kaufman","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.brainres.2006.09.101_bib20","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1177\/030098589703400405","article-title":"Neuronal vacuolation and spinocerebellar degeneration in young Rottweiler dogs","volume":"34","author":"Kortz","year":"1997","journal-title":"Vet. Pathol."},{"key":"10.1016\/j.brainres.2006.09.101_bib21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1172\/JCI111695","article-title":"Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. A model for the study of phenylalanine and brain function in man","volume":"75","author":"Krause","year":"1985","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.brainres.2006.09.101_bib22","series-title":"Robbins and Cotran Pathologic Basis of Disease","author":"Kumar","year":"2005"},{"key":"10.1016\/j.brainres.2006.09.101_bib23","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1073\/pnas.96.5.1811","article-title":"Phenylketonuria: old disease, new approach to treatment","volume":"96","author":"Levy","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.brainres.2006.09.101_bib24","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/jnr.10307","article-title":"Oxidative stress induced by phenylketonuria in the rat: prevention by melatonin, vitamin E, and vitamin C","volume":"69","author":"Martinez-Cruz","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.brainres.2006.09.101_bib25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/geno.1996.4508","article-title":"Characterization of mutations at the mouse phenylalanine hydroxylase locus","volume":"39","author":"McDonald","year":"1997","journal-title":"Genomics"},{"key":"10.1016\/j.brainres.2006.09.101_bib26","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/sj.gt.3301221","article-title":"Influence of promoter and WHV post-transcriptional regulatory element on AAV-mediated transgene expression in the rat brain","volume":"7","author":"Paterna","year":"2000","journal-title":"Gene Ther."},{"key":"10.1016\/j.brainres.2006.09.101_bib27","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/00019052-199812000-00012","article-title":"Neurological aspects of adult phenylketonuria","volume":"11","author":"Pietz","year":"1998","journal-title":"Curr. Opin. Neurol."},{"key":"10.1016\/j.brainres.2006.09.101_bib28","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1542\/peds.99.3.345","article-title":"Psychiatric disorders in adult patients with early-treated phenylketonuria","volume":"99","author":"Pietz","year":"1997","journal-title":"Pediatrics"},{"key":"10.1016\/j.brainres.2006.09.101_bib29","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1007\/s004310050945","article-title":"Neurological outcome in adult patients with early-treated phenylketonuria","volume":"157","author":"Pietz","year":"1998","journal-title":"Eur. J. Pediatr."},{"key":"10.1016\/j.brainres.2006.09.101_bib30","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1097\/00001756-200004270-00042","article-title":"Dramatic brain aminergic deficit in a genetic mouse model of phenylketonuria","volume":"11","author":"Puglisi-Allegra","year":"2000","journal-title":"NeuroReport"},{"key":"10.1016\/j.brainres.2006.09.101_bib31","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1515\/BC.2002.044","article-title":"Nitric oxide and peroxynitrite interactions with mitochondria","volume":"383","author":"Radi","year":"2002","journal-title":"Biol. Chem."},{"key":"10.1016\/j.brainres.2006.09.101_bib32","doi-asserted-by":"crossref","unstructured":"Saravanan, K.S., Sindhu, K.M., Mohanakumar, K.P., 2005 Acute intranigral infusion of rotenone in rats causes progressive biochemical lesions in the striatum similar to Parkinson's disease, pp. 147\u2013155.","DOI":"10.1016\/j.brainres.2005.04.051"},{"key":"10.1016\/j.brainres.2006.09.101_bib33","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1006\/mthe.2000.0191","article-title":"Context dependence of different modules for posttranscriptional enhancement of gene expression from retroviral vectors","volume":"2","author":"Schambach","year":"2000","journal-title":"Mol. Ther."},{"key":"10.1016\/j.brainres.2006.09.101_bib34","series-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Scriver","year":"1995"},{"key":"10.1016\/j.brainres.2006.09.101_bib35","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/genetics\/134.4.1205","article-title":"Mouse models of human phenylketonuria","volume":"134","author":"Shedlovsky","year":"1993","journal-title":"Genetics"},{"key":"10.1016\/j.brainres.2006.09.101_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-8981(98)00091-6","article-title":"Antioxidant status in hyperphenylalaninemia","volume":"276","author":"Sierra","year":"1998","journal-title":"Clin. Chim. Acta"},{"key":"10.1016\/j.brainres.2006.09.101_bib37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbadis.2005.02.005","article-title":"Oxidative stress in patients with phenylketonuria","volume":"1740","author":"Sirtori","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.brainres.2006.09.101_bib38","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/S0140-6736(74)91873-X","article-title":"Natural history of phenylketonuria and influence of early treatment","volume":"2","author":"Smith","year":"1974","journal-title":"Lancet"},{"key":"10.1016\/j.brainres.2006.09.101_bib39","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/sj.gt.3301422","article-title":"Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal vein injection of recombinant adeno-associated virus (rAAV) vectors","volume":"8","author":"Song","year":"2001","journal-title":"Gene Ther."},{"key":"10.1016\/j.brainres.2006.09.101_bib40","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1212\/WNL.34.9.1246","article-title":"Phenylalanine and phenylacetate adversely affect developing mammalian brain neurons","volume":"34","author":"Swaiman","year":"1984","journal-title":"Neurology"},{"key":"10.1016\/j.brainres.2006.09.101_bib41","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1023\/B:BOLI.0000037353.13085.e2","article-title":"The role of oxidative damage in the neuropathology of organic acidurias: insights from animal studies","volume":"27","author":"Wajner","year":"2004","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.brainres.2006.09.101_bib42","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1023\/A:1010912929042","article-title":"Nitric oxide synthase inhibition by L-NAME prevents the decrease of Na+, K+-ATPase activity in midbrain of rats subjected to arginine administration","volume":"26","author":"Wyse","year":"2001","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.brainres.2006.09.101_bib43","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1096\/fj.03-0983fje","article-title":"Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase","volume":"18","author":"Zhang","year":"2004","journal-title":"FASEB J."},{"key":"10.1016\/j.brainres.2006.09.101_bib44","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S1046-2023(02)00220-7","article-title":"Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors","volume":"28","author":"Zolotukhin","year":"2002","journal-title":"Methods"}],"container-title":["Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899306028587?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006899306028587?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T20:03:38Z","timestamp":1628107418000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006899306028587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1]]},"references-count":44,"alternative-id":["S0006899306028587"],"URL":"https:\/\/doi.org\/10.1016\/j.brainres.2006.09.101","relation":{},"ISSN":["0006-8993"],"issn-type":[{"value":"0006-8993","type":"print"}],"subject":[],"published":{"date-parts":[[2007,1]]}}}