Publications by authors named "Prasada Rao S Kodavanti"

The US EPA's Toxicity Forecaster (ToxCast) is a suite of high-throughput in vitro assays to screen environmental toxicants and predict potential toxicity of uncharacterized chemicals. This work examines the relevance of ToxCast assay intended gene targets to putative molecular initiating events (MIEs) of neurotoxicants. This effort is needed as there is growing interest in the regulatory and scientific communities about developing new approach methodologies (NAMs) to screen large numbers of chemicals for neurotoxicity and developmental neurotoxicity.

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Individuals with psychosocial stress often experience an exaggerated response to air pollutants. Ozone (O) exposure has been associated with the activation of the neuroendocrine stress-response system. We hypothesized that preexistent mild chronic stress plus social isolation (CS), or social isolation (SI) alone, would exacerbate the acute effects of O exposure on the circulating adrenal-derived stress hormones, and the expression of the genes regulating glucocorticoid stress signaling via an altered stress adaptation in a brain-region-specific manner.

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During the past century, a vast number of organic chemicals have been manufactured and used in industrial, agricultural, public health, consumer products, and other applications. The widespread use in bulk quantities of halogenated organic chemicals (HOCs; also called Organohalogens), including chlorinated, brominated, and fluorinated compounds, and their persistent nature have resulted in global environmental contamination. Increasing levels of HOCs in environmental media (i.

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Exposure to a prototypic air pollutant ozone (O) has been associated with the activation of neuroendocrine stress response along with neural changes in oxidative stress (OS), inflammation, and Alzheimer's disease-like pathologies in susceptible animal models. We hypothesized that neural oxidative and transcriptional changes induced by O in stress responsive regions are sex-dependent. Male and female adult Long-Evans rats were exposed to filtered air or O for two consecutive days (0.

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Psychosocially-stressed individuals might have exacerbated responses to air pollution exposure. Acute ozone exposure activates the neuroendocrine stress response leading to systemic metabolic and lung inflammatory changes. We hypothesized chronic mild stress (CS) and/or social isolation (SI) would cause neuroendocrine, inflammatory, and metabolic phenotypes that would be exacerbated by an acute ozone exposure.

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Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring.

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Air pollution has been associated with metabolic diseases and hepatic steatosis-like changes. We have shown that ozone alters liver gene expression for metabolic processes through neuroendocrine activation. This study aimed to further characterize ozone-induced changes and to determine the impact of hepatic vagotomy (HV) which reduces parasympathetic influence.

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A critical part of community based human health risk assessment following chemical exposure is identifying sources of susceptibility. Life stage is one such susceptibility. A prototypic air pollutant, ozone (O) induces dysfunction of the pulmonary, cardiac, and nervous systems.

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Ozone (O) is a widespread air pollutant that produces cardiovascular and pulmonary dysfunction possibly mediated by activation of central stress centers. Epidemiological data suggest that sedentary lifestyles may exacerbate responses to air pollutants such as O. We sought to assess neurological changes in response to O exposure and an active lifestyle.

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The Hard-Soft Acid and Base hypothesis can be used to predict the potential bio-reactivity (electrophilicity) of a chemical with intracellular proteins, resulting in neurotoxicity. Twelve chemicals predicted to be neurotoxic were evaluated in vitro in rat dorsal root ganglia (DRG) for effects on cytotoxicity (%LDH), neuronal structure (total neurite length/neuron, NLPN), and neurophysiology (mean firing rate, MFR). DRGs were treated acutely on days in vitro (DIV) 7 (1-100 μM) with test chemical; %LDH and NLPN were measured after 48 h.

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Mitochondria play a central role in energy homeostasis and act as regulatory checkpoints for downstream metabolic responses and cell senescence processes during an entire life span. Acute or chronic environmental toxicant exposures have shown deleterious organ-specific human health issues at various life stages. Since mitochondria are a prime target for ensuing cellular bioenergetics responses and senescence, it is essential to understand mitochondrial bioenergetic responses in different organs over multiple life stages.

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Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants considered as neurotoxicants and endocrine disruptors with important biological effects ranging from alterations in growth, reproduction, and effects on the hypothalamus-pituitary-adrenal axis. The vasopressinergic (AVPergic) system is a known target for pentaBDEs mixture (DE-71) and the structurally similar chemicals, polychlorinated biphenyls. However, the potential adverse effects of mixtures containing octaBDE compounds, like DE-79, on the AVPergic system are still unknown.

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Dietary supplementation with omega-3 and omega-6 fatty acids offer cardioprotection against air pollution, but these protections have not been established in the brain. We tested whether diets rich in omega-3 or -6 fatty acids offered neuroprotective benefits, by measuring mitochondrial complex enzyme I, II and IV activities and oxidative stress measures in the frontal cortex, cerebellum, hypothalamus, and hippocampus of male rats that were fed either a normal diet, or a diet enriched with fish oil olive oil, or coconut oil followed by exposure to either filtered air or ozone (0.8 ppm) for 4 h/day for 2 days.

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Oxidative stress (OS) contributes to the neurological and cardio/pulmonary effects caused by adverse metabolic states and air pollutants such as ozone (O₃). This study explores the interactive effects of O₃ and diet (high-fructose (FRUC) or high⁻fat (FAT)) on OS in different rat brain regions. In acute exposure, there was a decrease in markers of reactive oxygen species (ROS) production in some brain regions by diet and not by O₃.

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Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are environmental pollutants that produce neurotoxicity and neuroendocrine disruption. They affect the vasopressinergic system but their disruptive mechanisms are not well understood. Our group reported that rats perinatally exposed to Aroclor-1254 (A1254) and DE-71 (commercial mixtures of PCBs and PBDEs) decrease somatodendritic vasopressin (AVP) release while increasing plasma AVP responses to osmotic activation, potentially emptying AVP reserves required for body-water balance.

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Accumulating evidence suggests a deleterious role for urban air pollution in central nervous system (CNS) diseases and neurodevelopmental disorders. Microglia, the resident innate immune cells and sentinels in the brain, are a common source of neuroinflammation and are implicated in air pollution-induced CNS effects. While renewable energy, such as soy-based biofuel, is of increasing public interest, there is little information on how soy biofuel may affect the brain, especially in people with preexisting disease conditions.

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Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group).

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The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute and one subchronic, were conducted to seek effects of the VOC, toluene, in rats and to compare the effects between acute and subchronic exposures. Adult male Long-Evans rats were exposed to toluene vapor (n=6 per group) at a concentration of 0 or 1019 ± 14 ppm for 6h in the acute study and at 0 ± 0, 10 ± 1.

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Background: Polybrominated diphenyl ethers (PBDEs) are structurally similar to polychlorinated biphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motor dysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular and molecular mechanisms for these neurotoxic effects are not fully understood; however, several studies have shown that PBDEs affect thyroid hormones, cause oxidative stress, and disrupt Ca2+-mediated signal transduction. Changes in these signal transduction pathways can lead to differential gene regulation with subsequent changes in protein expression, which can affect the development and function of the nervous system.

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Polybrominated diphenyl ether BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) is a thyroid hormone disruptor in mice; hepatic induction of various metabolic enzymes and transporters has been suggested as the mechanism for this disruption. Utilizing Car (-/-) and Pxr (-/-) mice as well as human primary hepatocytes, here we have demonstrated that BDE-47 activated both mouse and human nuclear receptor constitutive activated/androstane receptor (CAR). In mouse livers, CAR, not PXR, was responsible for Cyp2b10 mRNA induction by BDE-47.

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Differential susceptibility to environmental exposures across life stages is an area of toxicology about which little is known. We examined the effects of toluene on transcriptomic changes and oxidative stress (OS) parameters (e.g.

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Polybrominated diphenyl ethers (PBDEs) and the structurally similar chemicals polychlorinated biphenyls (PCBs) disrupt the function of multiple endocrine systems. PCBs and PBDEs disrupt the secretion of vasopressin (VP) from the hypothalamus during osmotic activation. Since the peripheral and central vasopressinergic axes are critical for osmotic and cardiovascular regulation, we examined whether perinatal PBDE exposure could impact these functions during physiological activation.

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Cell signaling is a complex process which controls basic cellular activities and coordinates actions to -maintain normal cellular homeostasis. Alterations in signaling processes have been associated with -neurological diseases, such as Alzheimer's and cerebellar ataxia, as well as cancer, autoimmunitiy, and diabetes. Recent evidence also indicates a role for signaling molecules in the adverse effects associated with the exposure to environmental chemicals.

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There is a growing concern about the effects of chemicals on the developing nervous system. Chemical exposure at critical periods of development can be associated with effects ranging from subtle to profound on the structure and/or function of the nervous system. Understanding critical biological molecular targets, which underlie chemical-induced neurotoxicity, will provide a scientific basis for risk assessment.

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The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca(2+)-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity.

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