Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity.
Gliosis is a universal response of the brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in the brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in the brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH(3)-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acute gliosis can be non-invasively imaged and quantified in the brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity.
Ho
Gideon
G
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, the Nanos, #04-01, 138669, Singapore.
Zhang
Chunyan
C
Zhuo
Lang
L
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005453:Fluorescence; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000175:diagnosis*; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020258:Neurotoxicity Syndromes / Q000175:diagnosis* / Q000209:etiology; D009498:Neurotoxins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase; D007608:Kainic Acid