Modulation of N-Methyl-D-Aspartate Receptors (NMDAR), Bcl-2 and C-Fos Gene Expressions on Exposure to Individual and Mixtures of Low Concentration Metals in Zebrafish (Danio rerio)

Abstract

Currently, there is limited information on the toxicity of low concentration of metal mixtures in the environment. Of particular interest is the effect of low levels of metal mixtures on neurodevelopment of aquatic organisms. This study reports the neurological gene expressions after exposing zebrafish embryos to low concentration toxic heavy metals, 120 h post fertilization (hpf). Embryos were exposed to low concentration individual and mixtures of lead (Pb), mercury (Hg), arsenic (As), and cadmium (Cd). Quantitative real-time PCR was used to assess gene expressions. The findings of this study confirmed that exposure to low concentration heavy metals upregulated N-methyl-D-aspartate (NMDA) receptor subunits NMDAR2A (NR2A), NMDAR2B (NR2B), and NMDAR2D (NR2D) and B cell lymphoma (Bcl-2) genes. NR2A genes were significantly upregulated by 90 and 74%, respectively, on exposure to Pb + As and Pb + Cd. NR2B genes were upregulated by 85.3, 68.6, 62.7, and 62.7% on exposure to As, Pb + Hg, Pb + As, and Pb + Cd, respectively. Exposure to As, Pb + Cd, and Pb + Hg + As significantly upregulated Bcl-2 genes by 2.01-, 1.84-, and 1.80-fold, respectively. NR1A and C-fos gene expressions were not significantly different from control. Upregulation of NMDAR subunits and Bcl-2 genes in this study was largely a counter measure against insults from exposure to low concentration heavy metals. Principal component analysis confirmed the influence of low concentration individual and mixtures of Pb, Hg, As, and Cd on gene expression of NMDAR subunits and Bcl-2. These data suggest that altered expression of NMDA receptor subunits and Bcl-2 genes may explain toxicity of low concentration individual and mixtures of Pb, Hg, As, and Cd.

Intraventricular infusion of quinolinic acid impairs spatial learning and memory in young rats: a novel mechanism of lead-induced neurotoxicity

“…An increase in the synaptic NR2B-containing receptor without any change in the overall cellular level of NR2B in response to Pb exposure has been reported [ 47 , 49 ]. In the Zebrafish embryo, Pb decreased the expression of NR1 and had no effect on the expression of NR2B [ 50 ]. Further research is needed to elucidate the temporal and brain-region-specific changes in the expression of these subunits in response to QA administration.…”

Effects of C5a and Receptor CD88 on Glutamate and N-Methyl-D-Aspartic Acid Receptor Expression in the Mouse Model of Optic Neuromyelitis

“…N-Methyl-D-aspartic acid receptor (NMDAR) is a Glu receptor, which is often closely related to the occurrence of central neuroinflammatory demyelinating diseases such as multiple sclerosis and autoimmune encephalomyelitis. NMDAR2B plays an important role in glutamate-induced excitatory nerve injury, and its increased activity can induce excitatory nerve injury in oligodendrocytes, which mediates demyelination of the central nervous system and optic nerve [ 6 , 7 ]. Thus, its role in inflammatory demyelinating disease NMO has come into focus.…”