Prof. Xiaojuan Xu
Department of Psychology, Grand Valley State University, Allendale, USA
Title: Developmental Exposure to Methylmercury or Lead Produced Long-lasting Neurobehavioral Impairments
Abstract:
The developing nervous system is especially susceptible to the toxic effects of environmental contaminants, such as mercury and lead. Developmental exposures to mercury or lead have been shown to give rise to a wide range of neurobehavioral impairments, including learning impairments. These neurobehavioral impairments are potentially long-lasting, and the impact of developmental exposures to mercury or lead may be greater if the impairments are propagated across generations.
In the first set of experiments, we investigated the neurobehavioral effects of developmental exposure to methylmercury in adult zebrafish, as well as the persistence of those effects in the second and third generations of zebrafish developmentally exposed to methylmercury as embryos using avoidance conditioning as the behavioral paradigm.In Experiment 1, adult zebrafish hatched from embryos exposed to either no methylmercury or various concentrations of methylmercury were trained and tested for avoidance responses. The results showed that adult zebrafish hatched from embryos not exposed to methylmercury learned avoidance responses during training and exhibited significantly increased avoidance responses during testing. However, adult zebrafish hatched from embryos exposed to methylmercury were hyperactive, frequently swimming back and forth during training. These fish showed decreased avoidance responses as they became less hyperactive during testing. The data indicated that the higher the concentration of methylmercury exposure, the more severe the hyperactivity during training and the more severe the learning impairments.In Experiment 2, adult zebrafish, representing the second generation of those developmentally exposed to various concentrations of methylmercury as embryos, were trained and tested for avoidance responses. The results indicated that the second generation of zebrafish developmentally exposed to methylmercury as embryos showed no hyperactivity but exhibited persistent learning impairments.In Experiment 3, adult zebrafish, representing the third generation of those developmentally exposed to various concentrations of methylmercury as embryos, were trained and tested for avoidance responses. The results indicated that the third generation of zebrafish developmentally exposed to only the higher concentration of methylmercury as embryos showed persistent learning impairments.These experiments demonstrated that developmental exposure to methylmercury produced long-lasting hyperactivity and learning impairments, and learning impairments persisted for generations.
In the second set of experiments, we investigated the persistence of learning impairments in adult males and females of the third generation (F3) of zebrafish exposed to lead as embryos. In Experiment 4, adult F3 males of zebrafish exposed to various concentrations of lead as embryos were trained and tested for avoidance responses. The results showed that adult F3 males of zebrafish exposed to no lead as embryos learned avoidance responses during training and exhibited significantly increased avoidance responses during testing. However, adult F3 males of zebrafish exposed to lead as embryos showed persistent learning impairment, with no significant increases in avoidance responses from training to testing. In Experiment 5, adult F3 females of zebrafish exposed to the same exposure regimen as in Experiment 4 were trained and tested for avoidance responses. The results revealed that adult F3 females of zebrafish exposed to no lead as embryos learned avoidance responses and displayed significantly increased avoidance responses from training to testing. However, adult F3 females of zebrafish exposed to lead as embryos showed no significant changes in avoidance responses from training to testing. Thus, these two experiments demonstrate that learning impairments produced by developmental lead exposure persist for generations in both male and female zebrafish.
Biography:
Dr. Xiaojuan Xu is a full professor in the Department of Psychology at Grand Valley State University in Michigan, USA. Dr. Xu has conducted several lines of research, one of which focuses on the neural mechanisms mediating learning and memory, as well as how environmental contaminants impair learning. Due to the basic similarities between the nervous systems of humans and goldfish, and the ease of experimental manipulation of goldfish nervous systems, Dr. Xu has primarily used goldfish in her research, later extending it to zebrafish.
Through a series of studies, Dr. Xu’s research team produced convincing and strong evidence suggesting that activation of the N-methyl-D-aspartate (NMDA) receptor is required for avoidance learning to occur, and that nitric oxide (NO) initiates changes in the brain that maintain memory of fear conditioning in goldfish. In another series of studies, her research team found that mercury exposure produced learning impairments in older adult zebrafish at much lower concentrations and more severely compared to younger adult zebrafish. Furthermore, embryonic exposure to lead or mercury produced learning impairments that persisted for at least three generations, demonstrating that the effects of embryonic exposure to lead or mercury pass from parents to their offspring and even their grandchildren.
Dr. Xu has frequently published in high-ranking, prestigious, and impactful journals such as Behavioral Neuroscience, Psychopharmacology, Brain Research, Neurobiology of Learning and Memory, NeuroToxicology, and Neurotoxicology and Teratology. Her works have often been cited by other researchers.