Effects of polychlorinated biphenyl (PCB) exposure on response perseveration and ultrasonic vocalization emission in rat during development

The 3 major symptoms of autistic spectrum disorders include 1) social behavioral alterations, 2) problems in communication and 3) higher-order motoric deficits of perseveration and stereotyped movements. Previous work has shown that early developmental exposure to polychlorinated biphenyls (PCBs) alters rat pup social motivation and juvenile rat social recognition/investigation. The present work extends this previous research by examining how perinatal PCB exposure alters motoric functions and communication abilities at different stages of development. Action perseveration was examined using performance measures from a T-maze environment. Communication abilities were evaluated by monitoring ultrasound emission in rat pups during a brief isolation from the litter. T-maze learning and performance were significantly impaired in PCB exposed animals. Additionally, PCB exposure led to reduced ultrasound emission rates during brief isolation from the natal group. When combined with the previous work using the same developmental exposure regimen, it seems clear that PCB exposure at moderate doses can lead to alterations in 1) social behavior, 2) action choice and perseveration, and 3) communication abilities making it a potential candidate as an endocrine disruptor involved in the production of autistic spectrum disorder in the human population

Determining the Critical Window of Influence of PCB Perinatally on Behavioral and Hormonal Development in Sprague-Dawley Rat Pups

Polychlorinated biphenyls (PCB) had widespread use in the United States in commercial manufacturing in the United States until the late 1970s. Even though they were banned, measurable amounts can still be found in the environment and food sources. PCB has known effects on altering hormone development and behavior in the species Rattus norvegicus. To determine the most crucial developmental time of exposure to PCB in Sprague-Dawley rat pups, rat pups were exposed to PCB at differing weeks of either gestation period or the first postnatal week. Behavioral tests were performed for the different rat pups, as well as blood serum was analyzed for the concentration of thyroid hormone. This paper presents data for PCB exposed pups that were tested for play behavior on PND 22. Statistical tests were used to determine the week of PCB exposure with the greatest effects on the rat pups. The results are that exposure of PCB led to a significant increase in the play behavior of the pups. The dorsal contact play behavior was significantly altered by PCB, while the pin behavior was not significantly altered. The critical window for PCB exposure was not identified, but it can be seen that PCB alters dorsal contact behavior in exposed rat pups

Polychlorinated biphenyl exposure alters oxytocin receptor gene expression and maternal behavior in rat model

Polychlorinated biphenyl (PCB) is a persistent organic pollutant known to induce diverse molecular and behavioral alterations. Effects of PCB exposure could be transmitted to future generations via changes in behavior and gene expression. Previous work has shown that PCB-exposure can alter social behavior. The present study extends this work by examining a possible molecular mechanism for these changes. Pregnant rats (Sprague-Dawley) were exposed through diet to a combination of non-coplanar (PCB 47 - 2,20,4,40-tetrachlorobiphenyl) and coplanar (PCB 77 - 3,30,4,40- tetrachlorobiphenyl) congeners. Maternal care behaviors were examined by evaluating the rate and quality of nest building on the last 4 d of gestation and dam/pup interactions on postnatal days 1, 2, 4 and 6. On postnatal day 17, dams were euthanized and hypothalamic tissue was removed for expression analyses of the oxytocin receptor (OXTR) and cytochrome P450 1a1 (Cyp1a1). PCB altered nest building and maternal care behaviors. Specifically, there was a significant increase in time spent in low crouch and high crouch nursing posture on PND 4 and PND 6 respectively. Molecular analysis revealed that PCB exposure upregulated OXTR expression in the hypothalamus of dams. These results provide a possible molecular mechanism for PCB-induced changes in social interactions during early development

Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation

Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells’ apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems

A synthesis of ENSO effects on drylands in Australia, North America and South America

Fundamentally, El Niño Southern Oscillation (ENSO) is a climatic and oceanographic phenomenon, but it has profound effects on terrestrial ecosystems. Although the ecological effects of ENSO are becoming increasingly known from a wide range of terrestrial ecosystems (Holmgren et al., 2001), their impacts have been more intensively studied in arid and semiarid systems. In this brief communication, we summarize the main conclusions of a recent symposium on the effects of ENSO in these ecosystems, which was convened as part of the First Alexander von Humboldt International Conference on the El Niño Phenomenon and its Global Impact, in Guayaquil, Ecuador, from 16–20 May 2005. Participants in the symposium shared results and perspectives from research conducted in North and South America and Australia, regions where the ecological effects of ENSO have been studied in depth. Although the reports covered a wide array of organisms and ecological systems (Fig. 1), a recurring theme was the strong increase in rainfall associated with ENSO events in dry ecosystems (during the El Niño phase of the oscillation in the Americas and the La Niña phase in Australia). Because inter-annual variability in precipitation is such a strong determinant of productivity in arid and semiarid ecosystems, increased ENSO rainfall is crucial for plant recruitment, productivity and diversity in these ecosystems. Several long-term studies show that this pulse in primary productivity causes a subsequent increase in herbivores, followed by an increase in carnivores, with consequences for changes in ecosystem structure and functioning that can be quite complex

Expression of an S phase-stabilized version of the CDK inhibitor Dacapo can alter endoreplication

In developing organisms, divergence from the canonical cell division cycle is often necessary to ensure the proper growth, differentiation, and physiological function of a variety of tissues. An important example is endoreplication, in which endocycling cells alternate between G and S phase without intervening mitosis or cytokinesis, resulting in polyploidy. Although significantly different from the canonical cell cycle, endocycles use regulatory pathways that also function in diploid cells, particularly those involved in S phase entry and progression. A key S phase regulator is the Cyclin E-Cdk2 kinase, which must alternate between periods of high (S phase) and low (G phase) activity in order for endocycling cells to achieve repeated rounds of S phase and polyploidy. The mechanisms that drive these oscillations of Cyclin E-Cdk2 activity are not fully understood. Here, we show that the Drosophila Cyclin E-Cdk2 inhibitor Dacapo (Dap) is targeted for destruction during S phase via a PIP degron, contributing to oscillations of Dap protein accumulation during both mitotic cycles and endocycles. Expression of a PIP degron mutant Dap attenuates endocycle progression but does not obviously affect proliferating diploid cells. A mathematical model of the endocycle predicts that the rate of destruction of Dap during S phase modulates the endocycle by regulating the length of G phase. We propose from this model and our in vivo data that endo S phase-coupled destruction of Dap reduces the threshold of Cyclin E-Cdk2 activity necessary to trigger the subsequent G-S transition, thereby influencing endocycle oscillation frequency and the extent of polyploidy

Detection of biomarkers for filoviral infection with a silicon photonic resonator platform

This protocol describes the use of silicon photonic microring resonator sensors for detection of Ebola virus (EBOV) and Sudan virus (SUDV) soluble glycoprotein (sGP). This protocol encompasses biosensor functionalization of silicon microring resonator chips, detection of protein biomarkers in sera, preparing calibration standards for analytical validation, and quantification of the results from these experiments. This protocol is readily adaptable toward other analytes, including cytokines, chemokines, nucleic acids, and viruses. For complete details on the use and execution of this protocol, please refer to Qavi et al. (2022)