Astrocytes: Adaptive Responses to Low Doses of Neurotoxins

Abstract

This article assesses how astrocytes respond to numerous endogenous agonists and a wide variety of chemical stressors, including well-known neurotoxic agents such as lead and methylmercury, and drugs, within the context of dose-response relationships. In general, astrocytes displayed biphasic dose-response relationships from exposure to neurotoxic agents with temporal and quantitative features similar to hormetic dose responses. While the low-dose stimulatory responses have been viewed as a manifestation of a toxic response, this perspective is being broadly reconsidered and in some cases reinterpreted as being an indicator of an adaptive/protective response. These dose-response patterns are likely to have significant implications in a wide range of conditions affecting normal developmental processes, tumor development, adaptive responses to numerous environmental neurotoxins, and strategies for drug development for the treatment of neurodegenerative conditions.