Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity.

Abstract

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.

• Authors: Gideon Ho, Chunyan Zhang, Lang Zhuo
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 221 Issue 1 Pg. 76-85 (May 15 2007) ISSN: 0041-008X [Print] United States
• PMID: 17350065 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Agonists
• Glial Fibrillary Acidic Protein
• Neurotoxins
• RNA, Messenger
• Green Fluorescent Proteins
• Tyrosine 3-Monooxygenase
• Kainic Acid

Topics

• Animals
• Animals, Newborn
• Astrocytes (drug effects, metabolism, pathology)
• Blotting, Western
• Cerebral Ventricles (drug effects, metabolism, pathology)
• Diagnostic Imaging (methods)
• Excitatory Amino Acid Agonists (toxicity)
• Fluorescence
• Glial Fibrillary Acidic Protein (genetics, metabolism)
• Gliosis (chemically induced, diagnosis)
• Green Fluorescent Proteins (chemistry, genetics, metabolism)
• Hippocampus (drug effects, metabolism, pathology)
• Humans
• Immunohistochemistry (methods)
• Kainic Acid (toxicity)
• Mice
• Mice, Transgenic
• Microscopy, Confocal
• Neurotoxicity Syndromes (diagnosis, etiology)
• Neurotoxins (administration & dosage, chemistry, toxicity)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Substantia Nigra (drug effects, metabolism)
• Tyrosine 3-Monooxygenase (chemistry, metabolism)