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Biomedical subjects

Charles F Ide

Publications and source records attributed to Charles F Ide.

8 recordsLinked to original sources

Polychlorinated biphenyl exposure delays metamorphosis and alters thyroid hormone system gene expression in developing Xenopus laevis.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that disrupt thyroid hormone (TH) system function in numerous species. Previous studies have shown delayed metamorphosis in developing Xenopus laevis frogs exposed to PCBs, but the underlying molecular mechanisms have not been thoroughly investigated. In this research, developing X. laevis tadpoles were exposed to environmentally relevant concentrations (5, 50ppb) of Aroclor 1254 (A1254), a PCB mixture, dissolved in water and 0.25% dimethyl sulfoxide. Quantitative real-time reverse transcriptase polymerase chain reaction was used to measure expression of several TH system genes, other genes that regulate growth and development, and a xenobiotic response gene. Exposure to 50ppb A1254 significantly delayed metamorphosis and significantly altered gene expression of three thyroid system genes: transthyretin and types II and III deiodinase. Since all three genes regulate the amount of available, biologically active TH, PCB-induced changes in the expression of these genes may underlie alterations in metamorphic timing.

Animals↗

Aroclor 1254 impairs the hearing ability of Xenopus laevis.

In this study we assessed the effects of chronic, dietary exposure of Aroclor 1254 (A1254) on the hearing of Xenopus frogs. We used the auditory brainstem response (ABR) to assay changes in hearing physiology; ABR thresholds, as well as latency-intensity and amplitude-intensity profiles of the initial positive (P1) and negative (N1) peaks were measured. Two groups of animals that received 50 ppm and 100 ppm of A1254 in their diet from 5 days post-fertilization through metamorphosis were compared to a control group that received untreated chow. The results showed significant threshold elevations in the 3-4 kHz range and significantly delayed peak latencies and reduced amplitudes at these frequencies in A1254 treated animals as compared to control animals. These findings indicate that A1254 selectively damages the high-frequency sensorineural hearing system associated with the basilar papilla of frogs. This preferential damage may be related to inherent differences in the vulnerability of the basilar versus amphibian papilla in the frog. The overall results of this study are also consistent with the reported A1254-induced auditory deficits in mammals indicating that the basilar papilla of the Xenopus frog may serve as an effective model for studying the effects of A1254 on the auditory system.

Acoustic Stimulation↗

Auditory brainstem responses to airborne sounds in the aquatic frog Xenopus laevis: correlation with middle ear characteristics.

In this study we recorded auditory brainstem responses to airborne sounds to determine the hearing sensitivity of Xenopus laevis frogs and correlated their hearing profiles with middle ear characteristics. In newly metamorphosed frogs (body mass 0.5-0.76 gm, snout-vent length 17-20 mm) best hearing sensitivities were measured in the 2.4-2.8 kHz range, whereas optimal hearing sensitivity of older adults (body mass 18-90 gm; snout-vent length 57-100 mm) ranged from 1.0 to 1.2 kHz. Middle ear volumes reconstructed from serial sections showed approximate volume of 0.002 cc and 0.04-0.07 cc in newly metamorphosed and older frogs, respectively. This inverse frequency-volume relationship is consistent with the properties of an acoustic resonator indicating that differences in best hearing sensitivity are at least in part correlated to variation in middle ear volumes for airborne sounds. These results are consistent with peak frequency vibrational velocity profiles of Xenopus tympanic disk that have been shown to be dependent on underlying middle ear volumes and corroborate the occurrence of peak amplitudes of otoacoustic emissions in the 1.0-1.2 kHz region in adult Xenopus frogs.

Aging↗

Dietary exposure to Aroclor 1254 alters gene expression in Xenopus laevis frogs.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that contribute to worldwide health problems. Despite data associating PCBs with adverse health effects, decisions to clean up contaminated sites remain controversial. Cleanup decisions are typically based on risk assessment methods that are not sensitive enough to detect subtle changes in health. We have recently shown that gene expression signatures can serve as sensitive molecular biomarkers of exposure and related health effects. Our initial studies were carried out with developing Xenopus laevis tadpoles that were exposed to the PCB mixture Aroclor 1254 (A1254) for 2 days. A1254 was dissolved in dimethyl sulfoxide and added to the aquarium water for rapid loading of PCBs into the tadpole tissue. These studies showed that increases in the expression of specific genes occurred independent of adverse health effects, and decreases in specific genes correlated with the appearance of observable health effects, including decreased survival and gross morphological and behavioral abnormalities. In this report, we extend our previous work to test the use of gene expression signatures as biomarkers in frogs exposed to PCBs through the diet from early tadpole stages through metamorphosis. This work showed that chronic low-dose exposure to A1254 (24 ppm) in food produced tissue levels of 17 ppm and increased gene expression of nerve growth factor and proopiomelanocortin independent of adverse health effects. Exposure to higher doses of A1254 (200 ppm) produced tissue levels of 80 ppm and increased expression of p450 1A1, also, independent of adverse health effects. This work provides further evidence for the use of gene expression changes as biomarkers of exposure to PCBs.

Actins↗

Connexin 43 expression in glial cells of developing rhombomeres of Xenopus laevis.

Connexin 43 is a gap junctional protein found predominantly in astrocytes. In the mammalian nervous system, it appears to play an organizational role during neural development. In the current study, conducted on the frog, Xenopus laevis, we found that connexin 43 occurs in glial cells during development of rhombomeres and that its expression is spatially and temporally regulated. We used neural (2G9) and cell proliferation (BrdU) markers to identify the overall organization of Xenopus rhombomeres and then tracked expression of connexin 43 and glial fibrillary acidic protein, an intermediate filament protein known to mark glia during rhombomeric development. 2G9 was expressed in rhombomeric centers (ventricular concavities) and outlying neuropil regions, whereas BrdU-labeled cells marked boundary regions (ventricular convexities), as early as stage 35/36. These labeling patterns persisted through premetamorphic stages of hindbrain development. At stage 47, 2G9-labeled profiles were highlighted by the presence of connexin 43, and at stage 49/50, connexin 43-labeled profiles, i.e., rhombomeric centers and neuropil, as well as rhombomeric boundaries, not labeled by connexin 43, became immunoreactive to glial fibrillary acidic protein. Cells of rhombomeric center regions and their processes in the outlying neuropil co-expressed glial fibrillary acidic protein and connexin 43 at a time that is characterized by the emergence of hindbrain auditory neural circuitry. Glial fibrillary acidic protein positive glial cells that appeared at rhombomeric boundaries never expressed connexin 43, but rather appeared to physically bisect ventricular convexities into adjacent rhombomeric regions. Thus, glial cells that express connexin 43 in developing rhombomeric centers may be similar to radial glia, assisting in formation of neural circuitry, while glial cells that do not express connexin 43, situated at rhombomeric boundaries, may be involved in demarcating adjacent rhombomeres.

Animals↗

Gene expression patterns predict exposure to PCBs in developing Xenopus laevis tadpoles.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that pose global ecological and human health problems. Although it is well established that PCBs are associated with a variety of adverse health effects in wildlife and in humans, it is often difficult to determine direct cause-and-effect relationships between exposure and specific health outcomes. In this study, gene expression signatures were used to relate exposure to PCBs with altered physiological responses and/or specific health effects. Real-time PCR was used to measure gene expression levels for 10 genes in Xenopus laevis tadpoles (18 days postfertilization, PF) after acute exposure (2 days) to the PCB mixture Aroclor 1254. Specific gene expression signatures correlated with exposure and were predictive of adverse health effects. Exposure to low levels of Aroclor 1254 (5-50 ppb) significantly increased expression of six genes, independent of any health effects; exposure to midlevel concentrations (300-400 ppb) significantly decreased expression levels of two genes, NGF and beta-actin, prior to the onset of observable health effects; exposure to higher doses (500-700 ppb) significantly decreased NGF and beta-actin expression concomitant with the appearance of gross morphological abnormalities, behavioral deficits, and a statistically significant decrease in survival. This study expands upon our previous work that demonstrated an age-dependent susceptibility to Aroclor 1254 in Xenopus laevis tadpoles and that defined specific gene expression signatures as useful bioindicators of exposure and as predictors of overt or impending health effects.

Animals↗

Exposure to the polychlorinated biphenyl mixture Aroclor 1254 alters melanocyte and tail muscle morphology in developing Xenopus laevis tadpoles.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have damaging effects on both ecosystem and human health. Numerous studies have shown that exposure to PCBs can alter growth and development of aquatic organisms, including frogs. In this report, developing Xenopus laevis tadpoles were exposed to the PCB mixture Aroclor 1254. Tadpoles were exposed from 5 through 9 d postfertilization to either 0, 1, 10, 50, or 100 ppm Aroclor 1254. Exposure to an acute, high concentration of Aroclor 1254 (10, 50, and 100 ppm) caused statistically significant reductions in survival and body size. In addition, tadpoles exposed to these higher concentrations showed histological abnormalities, including aberrant tail tip, myotomal, and melanocyte morphologies. Described adverse health effects associated with PCB exposure of developing frogs will serve as useful health endpoints in ongoing and future molecular-based studies that correlate health effects with changes in gene expression.

Animals↗

Aroclor 1254 alters morphology, survival, and gene expression in Xenopus laevis tadpoles.

PCBs are persistent environmental contaminants that cause a variety of adverse health effects in wildlife and humans. This article describes the use of signature gene expression patterns that link increased PCB exposure with progressive, adverse biological effects. Developing Xenopus laevis tadpoles of two age classes were exposed to the PCB mixture Aroclor 1254 for 2 days. Real-time PCR was used to quantitate mRNA expression for 11 physiologically relevant, potential bioindicator genes. Younger tadpoles (5 days postfertilization) were resistant to Aroclor 1254 and showed few changes in gross morphology, swimming behavior, survival, or gene expression. Older tadpoles (11 days postfertilization) were more susceptible to Aroclor 1254. Exposure to 25 and 50 ppm Aroclor 1254 caused alterations in gross morphology and swimming behavior and statistically significant decreases in survival. These tadpoles showed statistically significant decreases in gene expression for 9 out of the 11 genes measured. Tadpoles exposed to 10 ppm showed incipient health changes but had gene expression profiles similar to the tadpoles treated with higher doses of Aroclor 1254. Tadpoles exposed to 1 ppm did not exhibit any observable adverse health effects, yet statistically significant decreases in gene expression occurred in these tadpoles (4 out of 11 genes). After prolonged exposure, tadpoles exposed to 1 and 10 ppm Aroclor 1254 exhibited health effects similar to those exposed to higher concentrations. Therefore, changes in expression of specific genes may serve not only as molecular bioindicators of Aroclor 1254 exposure but also as predictors of impending adverse health effects.

Animals↗