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QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.
Citation:
HARRILL, J. QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA. Presented at Society of Toxicology Annual Meeting, Waashington, DC, March 06 - 10, 2011.
Impact/Purpose:
This talk will focus on the development of high content assays which allowed concentration-response assessments of multiple chemicals in 96 well microtiter plates, in an efficient and cost-effective manner.
Description:
New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. While in vitro systems can not fully replicate the complex temporospatial development of the brain, neuronal cultures can recapitulate neurodevelopmental processes such as cell proliferation, differentiation, growth, and synaptogenesis. We have evaluated primary neural cultures as models for neurite outgrowth, estabalishment of polarity and synaptogenesis: processes critical for the development of neuronal connectivity. In primary neural cultures, these events occur sequentially, and the effects of chemicals on specific neurodevelopmental processes can be investigated using different developmental/exposure periods. This talk will focus on the development of high content assays which allowed concentration-response assessments of multiple chemicals in 96 well microtiter plates, in an efficient and cost-effective manner. The ability of these assays to detect effects on in vitro neural development was determined using a "training set" of chemicals with known effects in vitro. Specific effects on neurodevelopment processes could be separated from cytotoxic effects using parallel analysis of cell number and morphological measurements. The results demonstrate that HCA assays can rapidly quantify chemical effects in vitro, distinguish between specific effects on neurodevelopmental endpoints and nonspecific changes in cell health and provide comparative data on which developmental events are more sensitive to a particular chemical insult. This abstract does not necessarily reflect USEPA policy.