Astrocytes: adaptive responses to low doses of neurotoxins.
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.
Calabrese
Edward J
EJ
Environmental Health Sciences Division, School of Public Health, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu
D000222:Adaptation, Physiological; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D009369:Neoplasms / Q000473:pathology; D004364:Pharmaceutical Preparations / Q000008:administration & dosage
D004785:Environmental Pollutants; D004364:Pharmaceutical Preparations