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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Inducible and conditional activation of ERK5 MAP kinase rescues mice from cadmium-induced olfactory memory deficits.

Authors: Wang, Hao; Matsushita, Megumi T; Abel, Glen M; Storm, Daniel R; Xia, Zhengui

Published In Neurotoxicology, (2020 12)

Abstract: Cadmium (Cd) is a heavy metal that is one of the most toxic environmental pollutants throughout the world. We previously reported that Cd exposure impairs olfactory memory in mice. However, the underlying mechanisms for its neurotoxicity for olfactory function are not well understood. Since adult Subventricular zone (SVZ) and Olfactory Bulb (OB) neurogenesis contributes to olfaction, olfactory memory defects caused by Cd may be due to inhibition of neurogenesis. In this study, using bromodeoxyuridine (BrdU) labeling and immunohistochemistry, we found that 0.6 mg/L Cd exposure through drinking water impaired adult SVZ/OB neurogenesis in C57BL/6 mice. To determine if the inhibition of olfactory memory by Cd can be reversed by stimulating adult neurogenesis, we utilized the transgenic caMEK5 mouse strain to conditional stimulate of adult neurogenesis by activating the endogenous ERK5 MAP kinase signaling pathway. This was accomplished by conditionally induced expression of active MEK5 (caMEK5) in adult neural stem/progenitor cells. The caMEK5 mice were exposed to 0.6 mg/L Cd for 38 weeks, and tamoxifen was administered to induce caMEK5 expression and stimulate adult SVZ/OB neurogenesis during Cd exposure. Short-term olfactory memory test and sand-digging based, odor-cued olfactory learning and memory test were conducted after Cd and tamoxifen treatments to examine their effects on olfaction. Here we report that Cd exposure impaired short-term olfactory memory and odor-cued associative learning and memory in mice. Furthermore, the Cd-impaired olfactory memory deficits were rescued by the tamoxifen-induction of caMEK5 expression. This suggests that Cd exposure impairs olfactory function by affecting adult SVZ/OB neurogenesis in mice.

PubMed ID: 33039505 Exiting the NIEHS site

MeSH Terms: Animals; Association Learning; Behavior, Animal*; Cadmium Chloride; Cues; Disease Models, Animal; Enzyme Activation; Female; Lateral Ventricles/enzymology*; Lateral Ventricles/pathology; Lateral Ventricles/physiopathology; Memory*; Mice, Inbred C57BL; Mice, Transgenic; Mitogen-Activated Protein Kinase 7/genetics; Mitogen-Activated Protein Kinase 7/metabolism*; Neurogenesis*; Odorants; Olfaction Disorders/chemically induced; Olfaction Disorders/enzymology; Olfaction Disorders/physiopathology; Olfaction Disorders/prevention & control*; Olfactory Bulb/enzymology*; Olfactory Bulb/pathology; Olfactory Bulb/physiopathology; Olfactory Perception*; Smell*; Time Factors

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