Subchronic manganese exposure impairs neurogenesis in the adult rat hippocampus

Sherleen Xue Fu Adamson, Xubo Shen, Wendy Jiang, Vivien Lai, Xiaoting Wang, Jonathan H. Shannahan, Jason R. Cannon, Jinhui Chen, Wei Zheng

Research output: Contribution to journalArticle

Abstract

Adult neurogenesis takes place in the brain subventricular zone (SVZ) in the lateral walls of lateral ventricles and subgranular zone (SGZ) in the hippocampal dentate gyrus (HDG), and functions to supply newborn neurons for normal brain functionality. Subchronic Mn exposure is known to disrupt adult neurogenesis in the SVZ. This study was designed to determine whether Mn exposure disturbed neurogenesis within the adult HDG. Adult rats (10 weeks old) received a single dose of bromodeoxyuridine (BrdU) at the end of 4-week Mn exposure to label the proliferating cells. Immunostaining and cell counting data showed that BrdU(+) cells in Mn-exposed HDG were about 37% lower than that in the control (p < .05). The majority of BrdU(+) cells were identified as Sox2(+) cells. Another set of adult rats received BrdU injections for 3 consecutive days followed by 2- or 4-week Mn exposure to trace the fate of BrdU-labeled cells in the HDG. The time course studies indicated that Mn exposure significantly reduced the survival rate (54% at 2 weeks and 33% at 4 weeks), as compared with that in the control (80% at 2 weeks and 51% at 4 weeks) (p < .01). A significant time-dependent migration of newborn cells from the SGZ toward the granule cell layer was also observed in both control and Mn-exposed HDG. Triple-stained neuroblasts and mature neurons further revealed that Mn exposure significantly inhibited the differentiation of immature neuroblasts into mature neurons in the HDG. Taken together, these observations suggest that subchronic Mn exposure results in a reduced cell proliferation, diminished survival of adult-born neurons, and inhibited overall neurogenesis in the adult HDG. Impaired adult neurogenesis is likely one of the mechanisms contribute to Mn-induced Parkinsonian disorder.

Original languageEnglish (US)
Pages (from-to)592-608
Number of pages17
JournalToxicological Sciences
Volume163
Issue number2
DOIs
StatePublished - Jun 1 2018

Fingerprint

Parahippocampal Gyrus
Neurogenesis
Dentate Gyrus
Bromodeoxyuridine
Manganese
Rats
Hippocampus
Neurons
Lateral Ventricles
Brain
Cells
Time and motion study
Cell proliferation
Labels
Parkinsonian Disorders
Cell Movement
Cell Proliferation
Newborn Infant
Injections

Keywords

  • Adult neurogenesis
  • Dentate gyrus
  • Granule cell layer
  • Manganese
  • Subgranular zone

ASJC Scopus subject areas

  • Toxicology

Cite this

Adamson, S. X. F., Shen, X., Jiang, W., Lai, V., Wang, X., Shannahan, J. H., ... Zheng, W. (2018). Subchronic manganese exposure impairs neurogenesis in the adult rat hippocampus. Toxicological Sciences, 163(2), 592-608. https://doi.org/10.1093/toxsci/kfy062

Subchronic manganese exposure impairs neurogenesis in the adult rat hippocampus. / Adamson, Sherleen Xue Fu; Shen, Xubo; Jiang, Wendy; Lai, Vivien; Wang, Xiaoting; Shannahan, Jonathan H.; Cannon, Jason R.; Chen, Jinhui; Zheng, Wei.

In: Toxicological Sciences, Vol. 163, No. 2, 01.06.2018, p. 592-608.

Research output: Contribution to journalArticle

Adamson, SXF, Shen, X, Jiang, W, Lai, V, Wang, X, Shannahan, JH, Cannon, JR, Chen, J & Zheng, W 2018, 'Subchronic manganese exposure impairs neurogenesis in the adult rat hippocampus', Toxicological Sciences, vol. 163, no. 2, pp. 592-608. https://doi.org/10.1093/toxsci/kfy062
Adamson SXF, Shen X, Jiang W, Lai V, Wang X, Shannahan JH et al. Subchronic manganese exposure impairs neurogenesis in the adult rat hippocampus. Toxicological Sciences. 2018 Jun 1;163(2):592-608. https://doi.org/10.1093/toxsci/kfy062
Adamson, Sherleen Xue Fu ; Shen, Xubo ; Jiang, Wendy ; Lai, Vivien ; Wang, Xiaoting ; Shannahan, Jonathan H. ; Cannon, Jason R. ; Chen, Jinhui ; Zheng, Wei. / Subchronic manganese exposure impairs neurogenesis in the adult rat hippocampus. In: Toxicological Sciences. 2018 ; Vol. 163, No. 2. pp. 592-608.
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