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.
Environmental Health Sciences Division, School of Public Health, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu
Edward J
EJ
Calabrese
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