title: Aberrant Adult Neurogenesis in the Subventricular Zone-Rostral Migratory Stream-Olfactory Bulb System Following Subchronic Manganese Exposure.
abstract: Adult neurogenesis occurs in brain subventricular zone (SVZ). Our recent data reveal an elevated proliferation of BrdU(+) cells in SVZ following subchronic manganese (Mn) exposure in rats. This study was designed to distinguish Mn effect on the critical stage of adult neurogenesis, ie, proliferation, migration, survival and differentiation from the SVZ via the rostral migratory stream to the olfactory bulb (OB). Adult rats received a single ip-dose of BrdU at the end of 4-week Mn exposure to label proliferating cells. Immunostaining and cell-counting showed a 48% increase of BrdU(+) cells in Mn-exposed SVZ than in controls (P< .05). These BrdU(+) cells were identified as a mixed population of mainly GFAP(+) type-B neural stem cells, Nestin(+) type-C transit progenitor cells, DCX(+) migratory neuroblasts and Iba1(+) microglial cells. Another group of adult rats received 3 daily ip-injections of BrdU followed by subchronic Mn exposure. By 4-week post BrdU labeling, most of the surviving BrdU(+) cells in the OB were differentiated into NeuN(+) matured neurons. However, survival rates of BrdU/NeuN/DAPI triple-labeled cells in OB were 33% and 64% in Mn-exposed and control animals, respectively (P< .01). Infusion of Cu directly into the lateral ventricle significantly decreased the cell proliferation in the SVZ. Taken together, these results suggest that Mn exposure initially enhances the cell proliferation in adult SVZ. In the OB, however, Mn exposure significantly reduces the surviving adult-born cells and markedly inhibits their differentiation into mature neurons, resulting in an overall decreased adult neurogenesis in the OB.
authors.affiliation: *School of Health Sciences, Purdue University, West Lafayette, Indiana 47907; and wzheng@purdue.edu.
authors.forename: Sherleen
authors.initials: S
authors.lastname: Fu
authors.affiliation: *School of Health Sciences, Purdue University, West Lafayette, Indiana 47907; and.
authors.forename: Wendy
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, 46202.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: *School of Health Sciences, Purdue University, West Lafayette, Indiana 47907; and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zeng
authors.affiliation: *School of Health Sciences, Purdue University, West Lafayette, Indiana 47907; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cholger
authors.affiliation: *School of Health Sciences, Purdue University, West Lafayette, Indiana 47907; and.
authors.forename: Jason
authors.initials: J
authors.lastname: Cannon
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, 46202.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Chen
authors.affiliation: *School of Health Sciences, Purdue University, West Lafayette, Indiana 47907; and wzheng@purdue.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D000089662:Doublecortin Protein; D057967:Infusions, Intraventricular; D007274:Injections, Intraperitoneal; D020547:Lateral Ventricles / Q000187:drug effects* / Q000473:pathology; D008297:Male; D017895:Manganese Compounds; D055495:Neurogenesis / Q000187:drug effects*; D009830:Olfactory Bulb / Q000187:drug effects* / Q000473:pathology; D017207:Rats, Sprague-Dawley
chemical_list: D002712:Chlorides; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D017895:Manganese Compounds; C025340:manganese chloride
keywords: adult neurogenesis; copper.; manganese; olfactory bulb; rostral migratory stream; subventricular zone