Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

Chia-Yu Chang,Li-Chuan Lin,Jiunn-Jye Chuu,Kai-Lin Yang,Wan-Chen Tsai,How-Ran Guo,Tain-Junn Cheng

doi:10.1155/2015/159015

Abstract

Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

Highlights

Arsenic is one of the most common environmental contaminants in ground water, and chronic arsenic related health effects are endemic in populations exposed to contaminated water [1]
In the open field test, the motion tracking analysis demonstrated that the normal mice with As2O3 exposure had less motion tracking (Figure 2(a)) and significantly decreased total ambulatory time (∗P < 0.05) and increased time spent (∗P < 0.05) in all four corner zones (% corner frequency) only after 8 weeks of arsenic exposure (Figures 2(b) and 2(c))
We investigated whether subchronic arsenic exposure could induce or enhance anxiety- or depression-like behaviors through downregulation of brain-derived neurotrophic factor (BDNF)-Tropomyosin receptor kinase B (TrkB) signaling pathway

Summary

Introduction

Arsenic is one of the most common environmental contaminants in ground water, and chronic arsenic related health effects are endemic in populations exposed to contaminated water [1]. Recent animal studies suggest that neurons in the brain may be the major targets of arsenic neurotoxicity and show myelin damage, disappearance of axons, vacuolar degeneration, and loss of cell-cell junction. Arsenic exposure from drinking water containing 1-2 mg/L (approximately 0.1–0.2 mg/kg/day) has been shown to induce oxidative DNA damage in the brain [7,8,9,10]. While inorganic arsenic exposure has been correlated with impairments of new learning and recent memory, few studies have explored its effects on mood disorder such as anxiety and depression. Anxiety and depression are currently the most common and well-studied mood disorders in humans and are commonly coexistent [11]. It was proposed that anxiety and depression may be a neuroendocrine continuum, in which anxiety occurs first during the life course and major depressive episodes occurred later [12]

Objectives

Methods

Results

Conclusion