Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment

Abstract

Background: The impact of an inflammatory response, as well as interactions between the immune and nervous systems, are rapidly assuming major roles in neurodegenerative disease and injury. However, it is now appreciated that the exact nature of such responses can differ with each type of insult and interaction. More recently, neuroinflammation and the associated cellular response of microglia are being considered for their contribution to neurotoxicity of environmental agents; yet, so far, the inclusion of inflammatory end points into neurotoxicity assessment have relied primarily on relatively limited measures or driven by in vitro models of neurotoxicity. Objective: To present background information on relevant biological considerations of neuroinflammation and the microglia response demonstrating the complex integrative nature of these biological processes and raising concern with regards to translation of effects demonstrated in vitro to the in vivo situation. Specific points are addressed that would influence the design and interpretation of neuroinflammation with regards to neurotoxicology assessment. Conclusion: There is a complex and dynamic response in the brain to regulate inflammatory processes and maintain a normal homeostatic level. The classification of such responses as beneficial or detrimental is an oversimplification. Neuroinflammation should be considered as a balanced network of processes in which subtle modifications can shift the cells toward disparate outcomes. The tendency to overinterpret data obtained in an isolated culture system should be discouraged. Rather, the use of cross-disciplinary approaches to evaluate several end points should be incorporated into the assessment of inflammatory contributions to the neurotoxicity of environmental exposures.

Keywords::

• ageing
• immunotoxicology
• mercury
• microglia
• neurodegenerative disease
• neuroinflammation
• neurotoxicology

Acknowledgement

This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences under Project no. 1Z01ES101623-05.