Adult exposure to insecticides causes persistent behavioral and neurochemical alterations in zebrafish.
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2020-03
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Farmers are often chronically exposed to insecticides, which may present health risks including increased risk of neurobehavioral impairment during adulthood and across aging. Experimental animal studies complement epidemiological studies to help determine the cause-and-effect relationship between chronic adult insecticide exposure and behavioral dysfunction. With the zebrafish model, we examined short and long-term neurobehavioral effects of exposure to either an organochlorine insecticide, dichlorodiphenyltrichloroethane (DDT) or an organophosphate insecticide chlorpyrifos (CPF). Adult fish were exposed continuously for either two or 5 weeks (10-30 nM DDT, 0.3-3 μM CPF), with short- and long-term effects assessed at 1-week post-exposure and at 14 months of age respectively. The behavioral test battery included tests of locomotor activity, tap startle, social behavior, anxiety, predator avoidance and learning. Long-term effects on neurochemical indices of cholinergic function were also assessed. Two weeks of DDT exposure had only slight effects on locomotor activity, while a longer five-week exposure led to hypoactivity and increased anxiety-like diving responses and predator avoidance at 1-week post-exposure. When tested at 14 months of age, these fish showed hypoactivity and increased startle responses. Cholinergic function was not found to be significantly altered by DDT. The two-week CPF exposure led to reductions in anxiety-like diving and increases in shoaling responses at the 1-week time point, but these effects did not persist through 14 months of age. Nevertheless, there were persistent decrements in cholinergic presynaptic activity. A five-week CPF exposure led to long-term effects including locomotor hyperactivity and impaired predator avoidance at 14 months of age, although no effects were apparent at the 1-week time point. These studies documented neurobehavioral effects of adult exposure to chronic doses of either organochlorine or organophosphate pesticides that can be characterized in zebrafish. Zebrafish provide a low-cost model that has a variety of advantages for mechanistic studies and may be used to expand our understanding of neurobehavioral toxicity in adulthood, including the potential for such toxicity to influence behavior and development during aging.
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Hawkey, Andrew B, Lilah Glazer, Cassandra Dean, Corinne N Wells, Kathryn-Ann Odamah, Theodore A Slotkin, Frederic J Seidler, Edward D Levin, et al. (2020). Adult exposure to insecticides causes persistent behavioral and neurochemical alterations in zebrafish. Neurotoxicology and teratology, 78. p. 106853. 10.1016/j.ntt.2019.106853 Retrieved from https://hdl.handle.net/10161/29505.
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Theodore Alan Slotkin
We study the interaction of drugs, hormones and environmental factors with the developing organism, with particular emphasis on the fetal and neonatal nervous system. The role of biochemical factors mediating development of nerve cells and other types of tissue is a major thrust, since they influence the subsequent structural and physiological status of critical organ systems. Ongoing projects comprise five areas: (1) Mechanisms regulating development of synapses - role of endocrine and other trophic factors, intracellular messengers in developing cells, control of target organ differentiation by neural input; (2) Adverse effects of exogenous agents on development, with an emphasis on identification of mechanisms by which behavioral or physiological damage occurs - drugs of abuse (especially nicotine), hormonal imbalances, environmental contaminants (especially pesticides), food additives, intrauterine growth retardation, fetal and neonatal hypoxia; (3) Control of fetal and neonatal cardiovascular and respiratory function by the immature nervous system - normal physiological mechanisms, responses to stress, factors mediating the transition from fetal to neonatal function, reactivity during delivery, Sudden Infant Death Syndrome; (4) Breast cancer cell growth regulation - role of hormone and neurotransmitter receptors converging on common cell signaling mechanisms, and targeting of these receptors for cancer therapeutics.
Frederic J. Seidler
We study the effect of drugs, hormones and environmental factors on the intracellular and extracellular biochemical signals that govern the development of mammalian neural tissues, with particular emphasis on the biochemistry and molecular biology underlying control of replication, differentiation, synaptogenesis and onset of synaptic function. Ongoing projects comprise the following areas: (1) the role of endocrine and neurotrophic factors in transmitter and receptor choice by developing neurons; (2) effects of drugs of abuse, hormonal imbalances, environmental contaminants and fetal/neonatal hypoxia, on nervous system development; (3) control of fetal/neonatal cardiovascular and respiratory function by the immature nervous system, with particular emphasis on parturition and Sudden Infant Death Syndrome; (4) molecular mechanisms of brain dysfunction in the elderly (Alzheimer's Disease and Depression); (5) control of gene expression in developing cells by trophic factors that operate through defined second messenger systems and protooncogenes.
Research is directed toward understanding the interaction of drugs, hormones and environmental factors with the developing nervous system. The role of these factors in mediating development of nerve cells is a major effort as they influence the subsequent structural and functional state of nervous system and its targets. The approach is multidisciplinary. Ongoing projects involve three areas:
1. Mechanisms regulating the development of synapses and the role of endocrine and other trophic factors (i.e. neurotransmitters) in this regulation. Long-term structural and functional consequences of altered development are evaluated.
2. Adverse effects of exogenous agents on nervous system development, emphasizing the identification of mechanisms by which behavioral or physiological injury occurs. Under investigation are: Drugs of abuse (especially cocaine and nicotine), hormonal imbalances, environmental contaminants (pesticides, flame retardants, etc.), food additives, stress, intrauterine growth retardation and hypoxia.
3. Molecular mechanisms of human brain dysfunction in the elderly, specifically Alzheimer's disease and depression.
New directions are concentrating on neurotransmitter and hormonal regulation of cell differentiation and gene expression:
1. Neurotransmitter control of cell differentiation in the central nervous system. The role of transient receptor expression and transduction in effecting the switch from replication to differentiation and the molecular (epigenetic) mechanism underlying control of early immediate genes.
2. Consequence of early life exposures on subsequent development of adult decease. Altered vulnerabilities resulting from multiple exposure events (i.e. fetal nicotine x neonatal pesticide).
3. Establishing in vitro models to explore the mechanisms abnormalities.
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