{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T19:40:38Z","timestamp":1694115638887},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2008,7,26]],"date-time":"2008-07-26T00:00:00Z","timestamp":1217030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005504","name":"Black Metropolis Research Consortium","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005504","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>We previously reported that a single subcutaneous (s.c.) injection of the neurotoxicant, 1\u2010methyl\u20104\u2010(2\u2032\u2010methylphenyl)\u20101,2,3,6\u2010tetrahydropyridine or 2\u2032\u2010CH<jats:sub>3<\/jats:sub>\u2010MPTP, to postnatal day 4 (PD4) mice caused acute and transient gliosis in the brain, which can be noninvasively monitored during a course of 8 h immediately after the dosing [Ho, G., Zhang, C.Y., Zhuo, L., 2007. Non\u2010invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity. Toxicol. Appl. Pharmacol. 221, 76\u201385]. In the current study, we examined the consequence of PD4 mice receiving multiple injections (4 \u00d7 8 mg\/kg, s.c. in 2 h intervals) of the same neurotoxicant 24\u201372 h after the last injection. Here we showed that the multiple dosing scheme (with a higher cumulative dose) triggered a severe gliosis not only in the striatum and substantia nigra pars compacta (SNpc), but also in hippocampus and cerebellum when examined by noninvasive <jats:italic>in vivo<\/jats:italic> imaging and by immunohistochemistry (IHC), respectively, in the PD5 to PD7 mice. When neonates treated with the neurotoxicant at PD4 were allowed to develop to 10 weeks of age and examined with IHC, a majority of the dopaminergic (DA) neurons were found to be permanently depleted from the adult SNpc. Our findings suggest that neurotoxicant\u2010elicited neonatal gliosis can be used as an early molecular signature to predict the permanent loss of DA neurons in the developed brain. Since 2\u2032\u2010CH<jats:sub>3<\/jats:sub>\u2010MPTP is an inducer of Parkinsonism in mice, the molecular imaging method described here is a relatively simple and powerful tool for longitudinally studying the developmental aspect of Parkinsonism.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2008.07.012","type":"journal-article","created":{"date-parts":[[2008,7,27]],"date-time":"2008-07-27T08:10:26Z","timestamp":1217146226000},"page":"673-681","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular imaging reveals a correlation between 2\u2032\u2010CH<sub>3<\/sub>\u2010MPTP\u2010induced neonatal neurotoxicity and dopaminergic neurodegeneration in adult transgenic mice"],"prefix":"10.1002","volume":"26","author":[{"given":"Gideon","family":"Ho","sequence":"first","affiliation":[{"name":"Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos, #04\u201001 Singapore The Nanos 138669"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saravana","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos, #04\u201001 Singapore The Nanos 138669"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos, #04\u201001 Singapore The Nanos 138669"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin Ling","family":"Kng","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos, #04\u201001 Singapore The Nanos 138669"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lang","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos, #04\u201001 Singapore The Nanos 138669"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35072550"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(90)90225-C"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890110410"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20118"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000247740.47667.03"},{"key":"e_1_2_6_7_1","first-page":"716","article-title":"Age\u2010dependent effects of the 2\u2032\u2010methyl analog of 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine: prevention by inhibitors of monoamine oxidase B","volume":"273","author":"Finnegan K.T.","year":"1995","journal-title":"Pharmacol. 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