Invertebrate Neuroscience

, Volume 12, Issue 2, pp 93–102 | Cite as

HSP-4 endoplasmic reticulum (ER) stress pathway is not activated in a C. elegans model of ethanol intoxication and withdrawal

  • Ben Ient
  • Richard Edwards
  • Richard Mould
  • Matthew Hannah
  • Lindy Holden-DyeEmail author
  • Vincent O’Connor
Original Paper


Acute and chronic exposure of Caenorhabditis elegans to concentrations of ethanol in the range 250–350 mM elicits distinct behaviours. Previous genetic analysis highlights specific neurobiological substrates for these effects. However, ethanol may also elicit cellular stress responses which may contribute to the repertoire of ethanol-induced behaviours. Here, we have studied the effect of ethanol on an important arm of the cellular stress pathways, which emanates from the endoplasmic reticulum (ER) in response to several conditions including heat shock and chemical or genetic perturbations that lead to protein misfolding. HSP-4 is a heat shock protein and homologue of mammalian BiP. It is a pivotal upstream component of the ER stress response. Therefore, we used a C. elegans heat shock protein mutant, hsp-4, and a strain carrying a transcriptional reporter, Phsp-4::gfp, to test the role of the ER following chronic ethanol conditioning. We found no evidence for an overt ER response during acute or prolonged exposure to concentrations of ethanol that lead to defined ethanol-induced behaviours. Furthermore, whilst hsp-4 was strongly induced by tunicamycin, pre-exposure of C. elegans to low doses of tunicamycin followed by ethanol was not sufficient to induce an additive ER stress response. Behavioural analysis of an hsp-4 mutant indicated no difference compared to wild type in susceptibility to ethanol intoxication and withdrawal. There is a clear precedent for a significance of ER stress pathways particularly in clinical conditions associated with toxic or pathological effects of high doses of alcohol consumption. The concentrations of ethanol used in this C. elegans study equate to the highest blood alcohol levels measured in patients with chronic alcohol dependency. Taken together, these observations imply that the classic ER stress pathway in C. elegans is relatively refractory to induction by ethanol.


Ethanol Alcohol ER stress Heat shock protein Caenorhabditis elegans hsp-4 Alcohol dependency 



Ben Ient was supported by graduate scholarship funds from the MRC and the Gerald Kerkut Charitable Trust. Richard Mould was supported by the Biotechnology and Biological Sciences Research Council UK Grant no. BB/E022251/1. Some nematode strains used in this work were provided by the Caenorhabditis elegans Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR).

Conflict of interest



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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ben Ient
    • 1
  • Richard Edwards
    • 1
  • Richard Mould
    • 1
  • Matthew Hannah
    • 2
    • 3
  • Lindy Holden-Dye
    • 1
    Email author
  • Vincent O’Connor
    • 1
  1. 1.Centre for BiosciencesUniversity of SouthamptonSouthamptonUK
  2. 2.Division of Molecular NeuroendocrinologyNIMR, The RidgewayLondonUK
  3. 3.Virus Reference DepartmentHealth Protection AgencyLondonUK

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