Alternative flame retardants: Is it possible to use protein expression levels as a biomarker for the neurotoxic effect of compounds on learning and memory?

Abstract

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in textiles, plastics, wire insulation and automobiles. They are additive flame retardants, which makes them prone to diffusion into the air. Exposure via house dust and diffusion into the air together with the toxicological and persistent characteristics of PBDEs, PBDEs can be a danger to human health. It has been shown that PBDE-exposed animals and children have cognitive dysfunctions and decreased learning and memory. Certain PBDEs have been banned and a search for alternative flame retardants is ongoing. Learning and memory is based on changes in the efficacy and local geometry of synaptic connections and transmissions, called synaptic plasticity. A long-lasting increase in synaptic strength is called long-term potentiation (LTP) and is a measure for learning and memory. Suggested key-proteins involved in LTP are AMPA-R, NMDA-R, calmodulin and ERK1/2. Currently the neurotoxicity of substances is tested using animals. The animals are exposed to the substance, then sacrificed and have their hippocampus removed. The hippocampus is cut into slices and LTP is measured using electrodes. These steps require time and precision. This thesis will research if it is possible to use changes in certain protein expression as a measure for neurotoxicity (biomarker), like learning and memory. Lead (Pb2+), methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are known neurotoxic compounds with adverse health effects on learning and memory. They cause alterations in the neurotransmitter system, calcium homeostasis and enhance oxidative stress in neurons. Alterations in the expression of the suggested key-proteins were studied. No literature was found on AMPA-R, calmodulin and ERK1/2. NMDA-R subtypes were found to be altered by Pb2+ and MeHg but not by PCBs. Besides the suggested key-proteins, PKC was found to be disturbed by all three compounds. It is possible to assess neurotoxicity of compounds by measuring protein expression levels. A common protein affected by the studied neurotoxins is PKC. Besides PKC, two out of three showed alterations in NMDA-R subtype expression. It is likely not all compounds affect the same protein(s). Further research is needed with more neurotoxic compounds to compose a list of biomarker proteins and to develop a protocol to analyze when a compound affects learning and memory.