Glycogen synthase kinase-3/Shaggy mediates ethanol-induced excitotoxic cell death of Drosophila olfactory neurons.

Proceedings of the National Academy of Sciences of the United States of America
Rachael L French, U Heberlein

Abstract

It has long been known that heavy alcohol consumption leads to neuropathology and neuronal death. While the response of neurons to an ethanol insult is strongly influenced by genetic background, the underlying mechanisms are poorly understood. Here, we show that even a single intoxicating exposure to ethanol causes non-cell-autonomous apoptotic death specifically of Drosophila olfactory neurons, which is accompanied by a loss of a behavioral response to the smell of ethanol and a blackening of the third antennal segment. The Drosophila homolog of glycogen synthase kinase-3 (GSK-3)beta, Shaggy, is required for ethanol-induced apoptosis. Consistent with this requirement, the GSK-3beta inhibitor lithium protects against the neurotoxic effects of ethanol, indicating the possibility for pharmacological intervention in cases of alcohol-induced neurodegeneration. Ethanol-induced death of olfactory neurons requires both their neural activity and functional NMDA receptors. This system will allow the investigation of the genetic and molecular basis of ethanol-induced apoptosis in general and provide an understanding of the molecular role of GSK-3beta in programmed cell death.

References

Jan 1, 1986·Progress in Neuro-psychopharmacology & Biological Psychiatry·P R MartinM J Eckardt
Jan 1, 1994·Methods in Cell Biology·A H BrandN Perrimon
Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A TakashimaK Imahori
Jul 22, 1998·Progress in Neurobiology·C L FaingoldA Riaz
Oct 17, 1998·Progress in Neurobiology·F Fadda, Z L Rossetti
Apr 10, 1999·Archives of General Psychiatry·I AgartzD W Hommer
Jul 16, 1999·Neurochemistry International·K WirknerP Illes
Apr 17, 2001·Apoptosis : an International Journal on Programmed Cell Death·J W OlneyC Ikonomidou
Jun 8, 2001·Alcoholism, Clinical and Experimental Research·A Y SunG Y Sun
Feb 19, 2002·Neurochemistry International·Gary E Gibson, Hui Zhang
May 1, 2002·Alcoholism, Clinical and Experimental Research·J A ObernierF T Crews
Aug 15, 2002·Pharmacology, Biochemistry, and Behavior·Jennifer A ObernierFulton T Crews
Sep 27, 2002·Genesis : the Journal of Genetics and Development·Marc Bourouis
Mar 27, 2003·Alcoholism, Clinical and Experimental Research·Claudia I RuppW Wolfgang Fleischhacker
Oct 21, 2004·Clinical Pediatrics·Peter ScalIris Borowsky
Mar 11, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Irene CappuccioAndrea Caricasole
Apr 13, 2005·Current Biology : CB·Shouzhen XiaAnn-Shyn Chiang
Sep 6, 2005·Current Biology : CB·Africa CoutoBarry J Dickson
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Fred W WolfUlrike Heberlein

❮ Previous
Next ❯

Citations

Apr 28, 2012·Cell Death and Differentiation·P ChenJ M Abrams
Jan 10, 2013·Pharmacological Reviews·Chi-Tso ChiuDe-Maw Chuang
May 10, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anita V DevineniUlrike Heberlein
Feb 24, 2016·Frontiers in Molecular Neuroscience·Michael A Collins, Edward J Neafsey
Aug 4, 2009·Neurotoxicology·Edward D LevinAnnette Kirshner
Jun 2, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·George R FlentkeSusan M Smith
Oct 30, 2013·Addiction Biology·Raniero L Peru Y Colón de PortugalAdrian Rothenfluh
Jun 28, 2012·Addiction Biology·Alfredo GhezziNigel S Atkinson
Dec 24, 2013·Progress in Neurobiology·Ted Weita LaiYu Tian Wang
Jun 13, 2013·Current Opinion in Genetics & Development·Emily A Bates
Dec 17, 2009·Current Biology : CB·Anita V Devineni, Ulrike Heberlein
Feb 23, 2017·Alcoholism, Clinical and Experimental Research·Amy E AdkinsBrien P Riley
Sep 30, 2017·Journal of Neurochemistry·Gary J Iacobucci, Shermali Gunawardena
Oct 9, 2019·Alcoholism, Clinical and Experimental Research·Benjamin TroutwineNigel S Atkinson
Sep 2, 2016·Frontiers in Cellular Neuroscience·JianGang WangChengbiao Lu
Jan 2, 2021·Frontiers in Behavioral Neuroscience·Maggie M ChvilicekAdrian Rothenfluh
May 28, 2021·Addiction Biology·Annie ParkNigel S Atkinson
Jun 14, 2021·Alcoholism, Clinical and Experimental Research·Michelle BonillaMariano Loza-Coll

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis