Astrocytes play a crucial role in the CNS, supporting normal neuronal activity by maintaining CNS homeostasis and BMS-777607 chemical structure controlling the concentrations of neurotransmitters and ions in the extracellular space (Vernadakis 1988; Wang and Bordey 2008; Belanger and Magistretti 2009). Ethanol regulation of the heat shock cascade and gene expression in astrocytes, therefore, Inhibitors,research,lifescience,medical may have profound implications for neuronal physiology. While there has been no work directly addressing this issue, several studies have shown that HSPs are involved in protecting the brain

from a variety of insults, including ischemia and neurodegeneration (Yenari 2002). In particular, it was found that overexpression of HSP72 in astrocytes prior to ischemia prevented astrocytic glutamate transporter dysfunction

and subsequent neuronal death in the CA1 region of the hippocampus (Xu et al. 2010). These findings suggest that ethanol activation of the heat shock cascade and induction of the Hsp Inhibitors,research,lifescience,medical genes in astrocytes may actually protect nearby neurons from any deleterious effects of alcohol exposure, as well as from future insults. Future studies will Inhibitors,research,lifescience,medical investigate these secondary effects of alcohol on neurons in order to identify changes in astrocytic gene expression and pathways that may be associated with the neuroprotective effects of alcohol. Acknowledgments We thank Heather Durham (McGill Inhibitors,research,lifescience,medical University, Montreal, Quebec, Canada) for providing the Hsf1 constructs and Richard Voellmy (University of Miami, Miami, FL) for permission to use them. This work was supported by National Institutes of Health (NIH)/NIAAA grants (R21 AA018783) to N. L. H. Conflict of Interest None declared. Supporting Information Additional Supporting Information

may be found in the online version of this article: Figure S1. Primary cell cultures Inhibitors,research,lifescience,medical from embryonic mouse cortex result in almost pure astrocyte populations. Figure S2. Normalization with two different housekeeping genes does not affect ethanol-induced expression of Hsp70 in primary astrocyte culture. Figure S3. Efficiency of transfection of DNA constructs in primary culture of mouse astrocytes. Click here to view.(1.6M, out docx) Table S1. Genes significantly activated by acute ethanol (E, 60 mmol/L, 1 h) and heat shock (HS, 42°C, 1 h) in primary cultures of astrocytes. Click here to view.(109K, docx)
Pain is defined as an unpleasant sensory and emotional experience, associated with real or potential tissue damage (Merskey and Bogduk 1994) and including both physical (i.e., nociception which means the detection of pain-producing stimuli by primary sensory neurons) and affective aspects (i.e. suffering) (Kupers et al. 2005).