Cadmium Exposure Impairs Adult Hippocampal Neurogenesis

Author:

Wang Hao1,Abel Glen M1,Storm Daniel R2,Xia Zhengui1

Affiliation:

1. Toxicology Program, Department of Environmental and Occupational Health Sciences

2. Department of Pharmacology, University of Washington, Seattle, Washington 98195

Abstract

Abstract Cadmium (Cd) is an environmental pollutant of considerable interest throughout the world and potentially a neurotoxicant. Our recent data indicate that Cd exposure induces impairment of hippocampus-dependent learning and memory in mice. However, the underlying mechanisms for this defect are not known. The goal of this study was to determine if Cd inhibits adult neurogenesis and to identify underlying signaling pathways responsible for this impairment. Adult hippocampal neurogenesis is a process in which adult neural progenitor/stem cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate functional new neurons in the hippocampus which contributes to hippocampus-dependent learning and memory. However, studies concerning the effects of neurotoxicants on adult hippocampal neurogenesis and the underlying signaling mechanisms are limited. Here, we report that Cd significantly induces apoptosis, inhibits proliferation, and impairs neuronal differentiation in primary cultured aNPCs derived from the SGZ. In addition, the c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase signaling pathways are activated by Cd and contribute to its toxicity. Furthermore, we exposed 8-week-old male C57BL/6 mice to Cd through drinking water for 13 weeks to assess the effects of Cd on adult hippocampal neurogenesis in vivo. Cd treatment reduced the number of 5-week-old adult-born cells in the DG and impaired the differentiation of adult-born hippocampal neurons. These results suggest that Cd exposure impairs adult hippocampal neurogenesis both in vitro and in vivo. This may contribute to Cd-mediated inhibition of hippocampus-dependent learning and memory.

Funder

Universtiy of Washington Superfund Research Program

Publisher

Oxford University Press (OUP)

Subject

Toxicology

Reference76 articles.

1. Developmental and long-term neurobehavioral toxicity of low-level in-utero cadmium exposure in rats;Ali;Neurobehav. Toxicol. Teratol.,1986

2. Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5;Chen;Free Radic. Biol. Med.,2008

3. MAPK and mTOR pathways are involved in cadmium-induced neuronal apoptosis;Chen;J. Neurochem.,2008

4. Effects of cadmium on forearm bone density after reduction of exposure for 10 years in a Chinese population;Chen;Environ. Int.,2009

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