title: Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.
abstract: There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI.
authors.affiliation: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, United States.
authors.forename: Elise C
authors.initials: EC
authors.lastname: Cope
authors.affiliation: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, United States.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Morris
authors.affiliation: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, United States.
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Gower-Winter
authors.affiliation: Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL, United States; Department of Statistics, Florida State University, Tallahassee, FL, United States.
authors.forename: Naomi C
authors.initials: NC
authors.lastname: Brownstein
authors.affiliation: Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, United States; Program in Neuroscience, Florida State University College of Medicine, Tallahassee, FL, United States. Electronic address: cathy.levenson@med.fsu.edu.
authors.forename: Cathy W
authors.initials: CW
authors.lastname: Levenson
mesh_terms: D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology* / Q000523:psychology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003866:Depressive Disorder / Q000209:etiology / Q000517:prevention & control; D004032:Diet; D019587:Dietary Supplements; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D015032:Zinc
keywords: Brain trauma; Depression; Hippocampus; Neurogenesis; Neuronal precursor; Proliferation; Zinc