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Characterization of the MDCK cell line for screening neurotoxicants
1U.S. Environmental Protection Agency, National Health Effects and Environmental Research Laboratories, Research Triangle Park, North Carolina 27711, USA.
Abstract:
The adoption of cell culture models to screen putative neurotoxicants is recognized in view of the consequences of nerve damage by environmental chemicals. Developing cell culture models that mimic certain properties of the blood-brain barrier (BBB) would be especially useful in view of the barrier's strategic role in the neurotoxic process. The present study evaluates a kidney epithelial cell line for its functional and enzymatic resemblance to cerebral endothelial cells. Madin-Darby canine kidney (i.e., MDCK) cells display morphological (i.e., ultrastructurally defined tight junctions), enzymatic (acetylcholinesterase, butyrylcholinesterase, gamma-glutamyl transpeptidase, superoxide dismutase, alkaline phosphatase, lactate dehydrogenase), and antigenic cell markers (i.e., Factor VIII), also found in cerebral endothelial cells. In addition, MDCK cells develop electrical resistance which is increased in response to conditioned media from astroglial cell lines (i.e., C6). These results suggest that the MDCK cell line might be useful for identifying neurotoxic chemicals that affect BBB integrity through similar endpoints.
Insights
Madin-Darby canine kidney cells show functional similarities to brain endothelial cells, making them a potential model for testing neurotoxic chemicals affecting the blood-brain barrier (BBB). This research aids in developing better methods for neurotoxicity screening.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Environmental chemicals can cause nerve damage, necessitating reliable methods for screening neurotoxicants.
- Cell culture models mimicking the blood-brain barrier (BBB) are crucial for understanding neurotoxic processes.
Purpose of the Study:
- To evaluate a kidney epithelial cell line (MDCK) for its functional and enzymatic similarity to cerebral endothelial cells.
- To determine the potential of MDCK cells as a model for assessing neurotoxic chemicals impacting BBB integrity.
Main Methods:
- Assessed morphological characteristics, including ultrastructurally defined tight junctions.
- Analyzed enzymatic markers (e.g., acetylcholinesterase, gamma-glutamyl transpeptidase) and antigenic markers (Factor VIII).
- Measured electrical resistance and its response to astroglial cell-conditioned media.
Main Results:
- MDCK cells exhibited morphological, enzymatic, and antigenic markers consistent with cerebral endothelial cells.
- MDCK cells developed electrical resistance, which was enhanced by astroglial cell-conditioned media.
- These findings indicate functional parallels between MDCK cells and the BBB's endothelial component.
Conclusions:
- The Madin-Darby canine kidney (MDCK) cell line demonstrates significant resemblance to cerebral endothelial cells.
- MDCK cells show potential as a valuable in vitro model for identifying neurotoxicants that compromise blood-brain barrier integrity.