spargel, the PGC-1α homologue, in models of Parkinson disease in Drosophila melanogaster.
BACKGROUND
Parkinson disease (PD) is a progressive neurodegenerative disorder presenting with symptoms of resting tremor, bradykinesia, rigidity, postural instability and additional severe cognitive impairment over time. These symptoms arise from a decrease of available dopamine in the striatum of the brain resulting from the breakdown and death of dopaminergic (DA) neurons. A process implicated in the destruction of these neurons is mitochondrial breakdown and impairment. Upkeep and repair of mitochondria involves a number of complex and key components including Pink1, Parkin, and the PGC family of genes. PGC-1α has been characterized as a regulator of mitochondria biogenesis, insulin receptor signalling and energy metabolism, mutation of this gene has been linked to early onset forms of PD. The mammalian PGC family consists of three partially redundant genes making the study of full or partial loss of function difficult. The sole Drosophila melanogaster homologue of this gene family, spargel (srl), has been shown to function in similar pathways of mitochondrial upkeep and biogenesis.


RESULTS
Directed expression of srl-RNAi in the D. melanogaster eye causes abnormal ommatidia and bristle formation while eye specific expression of srl-EY does not produce the minor rough eye phenotype associated with high temperature GMR-Gal4 expression. Ddc-Gal4 mediated tissue specific expression of srl transgene constructs in D. melanogaster DA neurons causes altered lifespan and climbing ability. Expression of a srl-RNAi causes an increase in mean lifespan but a decrease in overall loco-motor ability while induced expression of srl-EY causes a severe decrease in mean lifespan and a decrease in loco-motor ability.


CONCLUSIONS
The reduced lifespan and climbing ability associated with a tissue specific expression of srl in DA neurons provides a new model of PD in D. melanogaster which may be used to identify novel therapeutic approaches to human disease treatment and prevention.
Department of Biology, Memorial University of Newfoundland, 232 Elizabeth Avenue, St. John's, NL, A1B 3X9, Canada. emvm45@mun.ca.
Eric M
EM
Merzetti
Department of Biology, Memorial University of Newfoundland, 232 Elizabeth Avenue, St. John's, NL, A1B 3X9, Canada. bestave@mun.ca.
Brian E
BE
Staveley
D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster; D008124:Locomotion / Q000235:genetics / Q000502:physiology*; D010300:Parkinson Disease / Q000235:genetics*; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; C527201:pgc protein, Drosophila; D042925:Positive Transcriptional Elongation Factor B