The Cellular and Molecular Progression of Mitochondrial Dysfunction Induced by Polybrominated Diphenyl Ether Flamer Retardant (PBDE) Pollutants
When Rachel Carson’s Silent Spring gave a prophetic warning of the deleterious effects of DDT pesticides on organisms and the environment, never did we realize that environmental pollutants would so heavily influence our development and our survival. One class of pollutants in particular, the PBDEs, is used as an additive in manufacturing to reduce combustion, and therefore to prevent the loss of human life and property. Exactly how PBDEs affect the development of vital escape circuitry, remains an area of intense study. Behavioral anomalies following exposure to one of the 209 different PBDE congeners have pioneered studies like ours seeking the primary mechanisms of action of PBDEs on neurobehavioral circuit connectivity. For example, newborn mice exposed to a high experimental dose of PBDEs (20 mg/kg/day) from post-natal day (PND) 2-15, showed delays in reaching behavioral milestones, decreased ability to even mount a response to startle-producing stimuli, and neurobehavioral anomalies, such as abnormal gait and rapid decreases in activity, continued into adulthood. Being able to sense danger and produce a proper startle response helps even young rats survive, yet these behavioral deficiencies in both detection and response are present in juveniles and continue into adulthood . After only acute neonatal exposure to PBDEs, life-long behavioral anomalies imply that PBDEs cause deficits in neural circuit development that negatively affect essential sensory and motor behavior pathways . Other common behavioral anomalies detected in short term PBDE-exposed neonatal mice included hyperactivity, or the ability to adapt to new stimuli, learning and memory deficits. Behind these behavioral deficits were reductions in nicotinic receptor populations likely at the neuromuscular junctions causing locomotor deficiencies, and in the hippocampus affecting memory. Neurotoxic properties of PBDEs showing increased rates of apoptosis and increased oxidative stress in hippocampal cell cultures lend support to the hippocampal receptor deficiencies and resulting behavioral deficits seen in mice . These significant studies in mice highlight how dangerous that even short-term exposure to PBDEs can be, especially during critical neural developmental periods that lead to life-long nervous system and behavioral problems. The main objective of this project is to utilize a simple yet powerful model organism, D. rerio, to understand the cellular and molecular mechanisms behind disruption of behavior circuit neurodevelopment by common and ubiquitous pollutants, PBDEs.
No prior lab expereince is needed. You must be willing to learn new methods in a lab setting.