Ultraviolet photolysis of chlorpyrifos: developmental neurotoxicity modeled in PC12 cells.

Background: Ultraviolet photodegradation products from pesticides form both in the field and during water treatment.

Objectives: We evaluated the photolytic breakdown of the organophosphate pesticide chlorpyrifos (CPF) in terms of both the chemical entities generated by low-pressure ultraviolet C irradiation and their potential as developmental neurotoxicants.

Methods: We separated by-products using high-performance liquid chromatography and characterized them by gas chromatography/mass spectrometry.

Exposure of neonatal rats to parathion elicits sex-selective reprogramming of metabolism and alters the response to a high-fat diet in adulthood.

Background: Developmental exposures to organophosphate pesticides are virtually ubiquitous. These agents are neurotoxicants, but recent evidence also points to lasting effects on metabolism.

Objectives: We administered parathion to neonatal rats.

Is fipronil safer than chlorpyrifos? Comparative developmental neurotoxicity modeled in PC12 cells.

Fipronil, a GABA(A) receptor antagonist, is replacing many insecticide uses formerly fulfilled by organophosphates like chlorpyrifos. Few studies have addressed the potential for fipronil to produce developmental neurotoxicity. We compared the neurotoxicity of fipronil and chlorpyrifos in undifferentiated and differentiating neuronotypic PC12 cells, evaluating indices of cell replication, cell number, differentiation, and viability for short- and long-term exposures.

Developmental neurotoxicity of perfluorinated chemicals modeled in vitro.

Background: The widespread detection of perfluoroalkyl acids and their derivatives in wildlife and humans, and their entry into the immature brain, raise increasing concern about whether these agents might be developmental neurotoxicants.

Objectives: We evaluated perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), and perfluorobutane sulfonate (PFBS) in undifferentiated and differentiating PC12 cells, a neuronotypic line used to characterize neurotoxicity.

Methods: We assessed inhibition of DNA synthesis, deficits in cell numbers and growth, oxidative stress, reduced cell viability, and shifts in differentiation toward or away from the dopamine (DA) and acetylcholine (ACh) neurotransmitter phenotypes.

Adolescent nicotine administration changes the responses to nicotine given subsequently in adulthood: adenylyl cyclase cell signaling in brain regions during nicotine administration and withdrawal, and lasting effects.

Neurodevelopmental vulnerability to nicotine extends into adolescence, the stage at which most smokers begin using tobacco. The "sensitization-homeostasis" model postulates that nicotine treatment permanently reprogrammes neural communication, so that underlying functional changes remain present despite the apparent restoration of behavioral normality. We administered nicotine to adolescent rats (postnatal days PN30-47) or adults (postnatal days PN90-107), using regimens that reproduce plasma levels in smokers, and assessed effects on the adenylyl cyclase (AC) signaling cascade, which is involved in nicotine dependence and withdrawal but also mediates numerous other neurotransmitter responses.

Ameliorating the developmental neurotoxicity of chlorpyrifos: a mechanisms-based approach in PC12 cells.

Background: Organophosphate developmental neurotoxicity involves multiple mechanisms converging on neural cell replication and differentiation.

Objectives: We evaluated mechanisms contributing to the adverse effects of chlorpyrifos (CPF) on DNA synthesis, cell number and size, and cell signaling mediated by adenylyl cyclase (AC) in PC12 cells, a neuronotypic cell line that recapitulates the essential features of developing mammalian neurons.

Results: In undifferentiated cells, cholinergic receptor antagonists had little or no protective effect against the antimitotic actions of CPF; however, when nerve growth factor was used to evoke differentiation, the antagonists showed partial protection against deficits in cell loss and alteration in cell size elicited by CPF, but were ineffective in preventing the deterioration of AC signaling.

Screening for developmental neurotoxicity using PC12 cells: comparisons of organophosphates with a carbamate, an organochlorine, and divalent nickel.

Background: In light of the large number of chemicals that are potential developmental neurotoxicants, there is a need to develop rapid screening techniques.

Objectives: We exposed undifferentiated and differentiating neuronotypic PC12 cells to different organophosphates (chlorpyrifos, diazinon, parathion), a carbamate (physostigmine), an organochlorine (dieldrin), and a metal (divalent nickel; Ni2+) and examined indices of cell replication and differentiation for both short- and long-term exposures.

Results: In undifferentiated cells, all the agents inhibited DNA synthesis, with the greatest effect for diazinon, but physostigmine eventually produced the largest deficits in the total number of cells after prolonged exposure.

Permanent, sex-selective effects of prenatal or adolescent nicotine exposure, separately or sequentially, in rat brain regions: indices of cholinergic and serotonergic synaptic function, cell signaling, and neural cell number and size at 6 months of age.

Nicotine is a neuroteratogen that disrupts neurodevelopment and synaptic function, with vulnerability extending into adolescence. We assessed the permanence of effects in rats on indices of neural cell number and size, and on acetylcholine and serotonin (5HT) systems, conducting assessments at 6 months of age, after prenatal nicotine exposure, adolescent exposure, or sequential exposure in both periods. For prenatal nicotine, indices of cell number and size showed few abnormalities by 6 months, but there were persistent deficits in cerebrocortical choline acetyltransferase activity and hemicholinium-3 binding to the presynaptic choline transporter, a pattern consistent with cholinergic hypoactivity; these effects were more prominent in males than females.

Japanese quail (Coturnix japonica) inseminations are more likely to fertilize eggs in a context predicting mating opportunities.

Theoretical developments in behavioural ecology have generated increased interest in the proximate mechanisms underlying fertilization, but little is known about how fertilization success is regulated by cues from the external or social environment in males and females. Here, we use a Pavlovian conditioning paradigm to show that inseminations resulting from mating male and female Japanese quail (Coturnix japonica) are more likely to fertilize eggs when they occur in a context predicting that an opposite-sex bird will appear than when they occur in a context predicting that an opposite-sex bird will not appear. This effect occurs when either the male or the female is the target of the conditioning.

Different colors reveal different information: how nutritional stress affects the expression of melanin- and structurally based ornamental plumage.

Avian plumage colors have emerged recently as model systems for investigating the types of information that can be signaled by showy sexual displays in animals. In many species, the brightness of carotenoid-based plumage reflects the health and condition of individuals and is used in mate selection. The information contained in melanin-based and structurally based ornamental colors in birds is less well resolved, however.