title: Trimethyltin intoxication induces the migration of ventricular/subventricular zone cells to the injured murine hippocampus.
abstract: Following the postnatal decline of cell proliferation in the mammalian central nervous system, the adult brain retains progenitor cells with stem cell-like properties in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampus. Brain injury can stimulate proliferation and redirect the migration pattern of SVZ precursor cells to the injury site. Sublethal exposure to the neurotoxicant trimethyltin (TMT) causes dose-dependent necrosis and apoptosis in the hippocampus dentate gyrus and increases SGZ stem cell proliferation to generate new granule cells. To determine whether SVZ cells also contribute to the repopulation of the TMT-damaged dentate gyrus, 6-8 week old male C3H mice were injected with the carbocyanine dye spDiI and bromodeoxyuridine (80mg/kg; ip.) to label ventricular cells prior to TMT exposure. The presence of labeled cells in hippocampus was determined 7 and 28days after TMT exposure. No significant change in the number of BrdU(+) and spDiI(+) cells was observed in the dentate gyrus 7days after TMT treatment. However, 28days after TMT treatment there was a 3-4 fold increase in the number of spDiI-labeled cells in the hippocampal hilus and dentate gyrus. Few spDiI(+) cells stained positive for the mature phenotypic markers NeuN or GFAP, suggesting they may represent undifferentiated cells. A small percentage of migrating cells were BrdU(+)/spDiI(+), indicating some newly produced, SVZ- derived precursors migrated to the hippocampus. Taken together, these data suggest that TMT-induced injury of the hippocampus can stimulate the migration of ventricular zone-derived cells to injured dentate gyrus.
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy and Joint Program in Toxicology, Rutgers Biomedical Health Sciences, Piscataway, NJ, United States.
authors.forename: Blair C
authors.initials: BC
authors.lastname: Weig
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy and Joint Program in Toxicology, Rutgers Biomedical Health Sciences, Piscataway, NJ, United States; Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, United States.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Richardson
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy and Joint Program in Toxicology, Rutgers Biomedical Health Sciences, Piscataway, NJ, United States.
authors.forename: Herbert E
authors.initials: HE
authors.lastname: Lowndes
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy and Joint Program in Toxicology, Rutgers Biomedical Health Sciences, Piscataway, NJ, United States. Electronic address: Reuhl@eohsi.rutgers.edu.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Reuhl
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D000596:Amino Acids; D005904:Glial Fibrillary Acidic Protein; D014298:Trimethyltin Compounds; C098463:dolaisoleucine; C046488:trimethyltin; D001973:Bromodeoxyuridine
keywords: Brain injury; Hippocampus; Neural stem cells; Neurogenesis; Subventricular stem cells; Trimethyltin