A chick model for the mechanisms of mustard gas neurobehavioral teratogenicity

Area of Science:

• Neuroscience
• Toxicology
• Developmental Biology

Background:

• Sulfur mustard (SM) is a chemical warfare agent known for its mutagenic and carcinogenic properties.
• Due to structural similarities with chemotherapy drugs like nitrogen mustard, SM is suspected to cause developmental neurotoxicity.
• Mammalian models can be confounded by maternal effects, necessitating alternative models for studying developmental neurotoxicants.

Purpose of the Study:

• To establish a chick model for investigating the mechanisms of sulfur mustard (SM)-induced neurobehavioral teratogenicity.
• To assess the effects of SM on imprinting behavior and related neurochemical changes in chicks.
• To provide a model free from mammalian maternal effects for evaluating SM's developmental toxicity.

Main Methods:

• Chicken eggs were injected with varying doses of sulfur mustard (SM) on incubation days 2 and 7.
• Posthatching, behavioral tests were conducted, focusing on imprinting behavior related to the hyperstriatum ventrale (IMHV).
• Levels of protein kinase C gamma (PKCgamma) in the IMHV were measured to assess neurochemical changes.

Main Results:

• Sulfur mustard (SM) exposure led to significant deficits in imprinting behavior in chicks.
• A decrease in membrane-bound PKCgamma was observed in the IMHV of SM-exposed chicks.
• No significant changes in cytosolic PKCgamma levels were detected, suggesting a specific impact on membrane-associated signaling.

Conclusions:

• The chick model is suitable for rapid evaluation of sulfur mustard (SM) behavioral teratogenicity.
• SM exposure impacts imprinting behavior by altering PKCgamma levels in the IMHV.
• This model can elucidate mechanisms of SM-induced neurobehavioral defects and inform future studies in both avian and mammalian systems.