Abstract
Cadmium (Cd), a widely existed environmental contaminant, was shown to trigger neurotoxicity by regulating autophagy, ion homeostasis and redox. Lycopene (LYC) is a natural substance with potent antioxidant capacity. Nevertheless, little is known about i) the relationship of Cd-induced neurotoxicity and autophagy, ion homeostasis as well as redox in the hippocampus; ii) the role of LYC in the regulation of hippocampal autophagy, ionic balance and antioxidant capacity during Cd exposure. Therefore, this study sought to investigate the Cd exposure-induced hippocampal dysfunctions for neurotoxicity, and the preventive potential of LYC on the hippocampus impairment by reversing the dysfunctions during the exposure. In vivo study with mice model demonstrated that Cd exposure increased gene expression of a wide spectrum of autophagy-related gene (ATG) and gene regulating autophagy in hippocampus. This suggests the activation of hippocampal autophagy mediated by Cd. Cd exposure also decreased Ca2+-ATPase activity, thus increasing intracellular Ca2+ concentration in hippocampus, indicating the possibility that Cd-induced autophagy requires the Ca2+ signaling. Moreover, Cd exposure triggered redox stress in hippocampus cells, as antioxidant enzyme activities were decreased while oxidative productions were promoted. Cd exposure led to severe cytotoxicity in hippocampus cells. Of important note, all the hippocampal dysfunctions upon Cd exposure were reversed by LYC treatment to normal situations, and exposure-induced neurotoxicity was abrogated. The in vivo findings were recapitulated relevantly in the mouse hippocampal neuronal cell line, TH22. In all, the above data imply that LYC could be a potent therapeutic agent in treating Cd-triggered hippocampal dysfunctions and subsequent cell damage.
Highlights
Cadmium (Cd) is recognized as an important environmental contaminant
Since Cd induces autophagy in mice brain [29], and induces autophagy by up-regulating autophagyrelated gene (ATG) [3], we sought to know if cadmium activates autophagy in hippocampus by modulating autophagy-related genes (ATGs) expressions
In vivo results showed in that a wide spectrum of ATG mRNA levels were up regulated in mice hippocampus exposed to cadmium, when compared to vehicle exposure
Summary
Cadmium (Cd) is recognized as an important environmental contaminant. It exists in environment through battery, circuit board, plastics and fertilizers. As an extremely toxic mental, Cd can cause severe toxicity in most organs, leading to organ-derived diseases. Cd can cause dysfunction of the central nervous system (CNS) after crossing the bloodbrain barrier, leading to many neurodegenerative diseases [3]. The neurotoxic effects may play www.impactjournals.com/oncotarget a role in the systemic toxic effects of the Cd exposure, the long-term exposure [4]. Hippocampus pathogenicity is a crucial factor contributing to most of the neurodegenerative diseases [5]. Previous reports demonstrated the impact of Cd on triggering hippocampal neurotoxicity [6, 7]
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