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The Journal of Neuroscience, June 18, 2008, 28(25):6419-6429; doi:10.1523/JNEUROSCI.1646-08.2008
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Neurobiology of Disease
Drosophila alicorn Is a Neuronal Maintenance Factor Protecting against Activity-Induced Retinal Degeneration
Milo R. Spasi
,1,2
Patrick Callaerts,1,3 andKoenraad K. Norga1,2 1Laboratory of Developmental Genetics, Flanders Institute for Biotechnology (VIB) 2Pediatric Hematology and Oncology Section, Department of Woman and Child, and 3Laboratory of Developmental Genetics, Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
Correspondence should be addressed to Dr. Koenraad K. Norga, Pediatric Hematology and Oncology, University of Leuven Children's Hospital, and Laboratory of Developmental Genetics, Flanders Institute for Biotechnology (VIB), 49 Herestraat, Mail Box 07003, B-3000 Leuven, Belgium. Email: koen.norga{at}uz.kuleuven.be
Exploring mechanisms that govern neuronal responses to metabolic stress is essential for the development of therapeutic strategies aimed at treatment of neuronal injury and disease. AMP-activated protein kinase (AMPK) is a key enzyme regulating cellular energy homeostasis that responds to changes in cellular energy levels by promoting energy-restorative and inhibiting energy-consumptive processes. Recent studies have suggested that AMPK might have a neuroprotective function. However, the existing evidence is contradictory and almost exclusively derived from in vitro studies based on drug treatments and metabolic stress models. To tackle these issues in vivo, we used the Drosophila visual system. In this report, we describe a novel Drosophila mutant, alicorn (alc), encoding the single β regulatory subunit of AMPK. Loss of alc using the eyFlp system causes severe early-onset progressive nonapoptotic neurodegeneration in the retina, the optic lobe, and the antennae, as well as behavioral and neurophysiological defects. Retinal degeneration occurs immediately after normal neuronal differentiation, can be enhanced by exposure to light, and can be prevented by blocking photoreceptor excitation. Furthermore, AMPK is required for proper viability of differentiated photoreceptors by mechanisms unrelated to polarity events that AMPK controls in epithelial tissues. In conclusion, AMPK does not affect photoreceptor development but is crucial to maintaining integrity of mature neurons under conditions of increased activity and provides protection from excitotoxicity.
Key words: AMPK; Drosophila; excitotoxicity; neurodegeneration; visual system; polarity
Received Feb. 25, 2008; revised May 5, 2008; accepted May 5, 2008.
Correspondence should be addressed to Dr. Koenraad K. Norga, Pediatric Hematology and Oncology, University of Leuven Children's Hospital, and Laboratory of Developmental Genetics, Flanders Institute for Biotechnology (VIB), 49 Herestraat, Mail Box 07003, B-3000 Leuven, Belgium. Email: koen.norga{at}uz.kuleuven.be
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