Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice. (4th May 2015)

• Record Type: Journal Article
• Authors: Kikuchihara, Yoh; Abe, Hajime; Tanaka, Takeshi; Kato, Mizuho; Wang, Liyun; Ikarashi, Yoshiaki; Yoshida, Toshinori; Shibutani, Makoto
• Is Part Of: Toxicology. Volume 331(2015)
• Page Start: 24
• Page End: 34
• Publication Date: 2015-05-04
• Subjects: AMPA alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- Arc activity-regulated cytoskeleton associated protein -- BDNF brain -derived neurotrophic factor -- c-Fos FBJ osteosarcoma oncogene -- Chrna4 cholinergic receptor, nicotinic, alpha polypeptide 4 -- Chrna7 cholinergic receptor, nicotinic, alpha polypeptide 7 -- Ct threshold cycle -- Dcx doublecortin -- GABA γ-aminobutyric acid -- GAD glutamic acid decarboxylase -- GCL granule cell layer -- GFAP glial fibrillary acidic protein -- Gria1 glutamate receptor, ionotropic, AMPA1 -- Gria2 glutamate receptor, ionotropic, AMPA2 (alpha 2) -- Gria3 glutamate receptor, ionotropic, AMPA3 (alpha 3) -- Grin2 aglutamate receptor, ionotropic, NMDA2A (epsilon 1) -- Grin2d glutamate receptor, ionotropic, NMDA2D (epsilon 4) -- Grm1 glutamate receptor, metabotropic 1 -- Hprt hypoxanthine-guanine phosphoribosyltransferase -- Mn manganese -- NeuN neuron-specific nuclear protein -- NMDA N-methyl-D-aspartate glutamate -- Ntrk2 neurotrophic tyrosine kinase, receptor, type 2 -- Pax6 paired box 6 -- PCNA proliferating cell nuclear antigen -- Pvalb parvalbumin -- SGZ subgranular zone -- Tbr2 T-box brain protein 2 -- TrkB tropomyosin-related kinase B receptor -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling; Manganese -- Hippocampal adult neurogenesis -- GABAergic interneuron -- BDNF; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2015.02.005
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: We examined the effect of oral Mn exposure on hippocampal neurogenesis in mice. 800-ppm Mn dietary exposure for 56 days, but not 28 days, disrupted neurogenesis. Reduction of Pvalb + interneurons may be responsible for the disrupted neurogenesis. Accumulated Mn may exert toxicity on granule cells to suppress neuronal plasticity. Suppression of granule cell BDNF-signaling may cause Pvalb + interneuron loss. Abstract: We previously found persistent aberration of hippocampal adult neurogenesis, along with brain manganese (Mn) accumulation, in mouse offspring after developmental exposure to 800-ppm dietary Mn. Reduction of parvalbumin (Pvalb) + γ-aminobutyric acid (GABA)-ergic interneurons in the hilus of the dentate gyrus along with promoter region hypermethylation are thought to be responsible for this aberrant neurogenesis. The present study was conducted to examine the relationship between the induction of aberrant neurogenesis and brain Mn accumulation after oral Mn exposure as well as the responsible mechanism in young adult animals. We used two groups of mice with 28- or 56-day exposure periods to oral MnCl2 · x H2 O at 800 ppm as Mn, a dose sufficient to lead to aberrant neurogenesis after developmental exposure. A third group of mice received intravenous injections of Mn at 5-mg/kg body weight once weekly for 28 days. The 28-day oral Mn exposure did not cause aberrations in neurogenesis. In contrast, 56-day oral exposure caused aberrations in neurogenesis suggestive of reductions in type 2b and type 3 progenitor cells and immature granule cells in the dentate subgranular zone. Brain Mn accumulation in 56-day exposed cases, as well as in directly Mn-injected cases occurred in parallel with reduction of Pvalb + GABAergic interneurons in the dentate hilus, suggesting that this may be responsible for aberrant neurogenesis. For reduction of Pvalb + interneurons, suppression of brain-derived neurotrophic factor-mediated signaling of mature granule cells may occur via suppression of c-Fos-mediated neuronal plasticity due to direct Mn-toxicity rather than promoter region hypermethylation of Pvalb .