Skin sensitization in silico protocol.

The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework.

Developmental pyrethroid exposure causes long-term decreases of neuronal sodium channel expression.

Pyrethroid insecticide use has increased over recent years because of their low to moderate acute toxicity in mammals. However, there is increasing concern over the potential detrimental effects of pyrethroids on developing animals. Most recently, we have shown that developmental exposure to deltamethrin results in long-term neurobehavioral effects.

Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol.

Ghrelin's receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons.

Role of calcium and calpain in the downregulation of voltage-gated sodium channel expression by the pyrethroid pesticide deltamethrin.

Voltage-gated sodium channels (Na(v)) are essential for initiation and propagation of action potentials. Previous in vitro studies reported that exposure to the Na(v) toxins veratridine and α scorpion toxin cause persistent downregulation of Na(v) mRNA in vitro. However the mechanism of this downregulation is not well characterized.

Channelopathies: summary of the hot topic keynotes session.

The "Hot Topic Keynotes: Channelopathies" session of the 26th International Neurotoxicology Conference brought together toxicologists studying interactions of environmental toxicants with ion channels, to review the state of the science of channelopathies and to discuss the potential for interactions between environmental exposures and channelopathies. This session presented an overview of chemicals altering ion channel function and background about different channelopathy models. It then explored the available evidence that individuals with channelopathies may or may not be more sensitive to effects of chemicals.

Developmental and activity-dependent regulation of ARMS/Kidins220 in cultured rat hippocampal neurons.

Neurotrophin activation of Trk receptors elicits diverse effects on neuronal survival, differentiation, and synaptic plasticity. One of the central questions is how specificity is encoded in neurotrophin receptor signaling and actions. A unique downstream protein is the Ankyrin-Repeat Rich Membrane Spanning (ARMS)/Kinase D-interacting substrate-220 kDa (Kidins220), a very abundant scaffold protein in the hippocampus.

Single-cell characterization of retrograde signaling by brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is a key regulator of hippocampal synaptic plasticity in the developing and adult nervous system. It can be released from pyramidal neuron dendrites in an activity-dependent manner and has therefore been suggested to serve as a signal that provides the retrograde intercellular communication necessary for Hebbian plasticity and hippocampal-dependent learning. Although much has been learned about BDNF function by field stimulation of hippocampal neurons, it is not known whether moderate action potential-independent depolarization of single cells is capable of releasing sufficient BDNF to influence transmission at individual synapses.