Reference Report

Reference
Citation	Daniels, R.W., Miller, B.R., Diantonio, A. (2011). Increased vesicular glutamate transporter expression causes excitotoxic neurodegeneration. Neurobiol. Disease 41(2): 415--420. (Export to RIS)
FlyBase ID	FBrf0212635
Publication Type	Research paper
PubMed ID	20951206
PubMed Abstract	Increases in vesicular glutamate transporter (VGLUT) levels are observed after a variety of insults including hypoxic injury, stress, methamphetamine treatment, and in genetic seizure models. Such overexpression can cause an increase in the amount of glutamate released from each vesicle, but it is unknown whether this is sufficient to induce excitotoxic neurodegeneration. Here we show that overexpression of the Drosophila vesicular glutamate transporter (DVGLUT) leads to excess glutamate release, with some vesicles releasing several times the normal amount of glutamate. Increased DVGLUT expression also leads to an age-dependent loss of motor function and shortened lifespan, accompanied by a progressive neurodegeneration in the postsynaptic targets of the DVGLUT-overexpressing neurons. The early onset lethality, behavioral deficits, and neuronal pathology require overexpression of a functional DVGLUT transgene. Thus overexpression of DVGLUT is sufficient to generate excitotoxic neuropathological phenotypes and therefore reducing VGLUT levels after nervous system injury or stress may mitigate further damage.
DOI	10.1016/j.nbd.2010.10.009
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Neurobiol. Disease
Title	Neurobiology of Disease
Publication Year	1994-
ISBN/ISSN	0969-9961
Data from Reference
Alleles (7)
	Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Scer\GAL4^BG380 Scer\GAL4^Orco.PK Scer\GAL4^VGlut.PD VGlut^{B44.Scer\UAS.T:Avic\GFP-EGFP} VGlut^Scer\UAS.cDa VGlut^{Scer\UAS.T:Avic\GFP-EGFP}
Constructs (6)
	P{Orco-GAL4.K} P{UAS-mCD8::GFP.L} P{UAS-VGlut.B44.GFP} P{UAS-VGlut.D} P{UAS-VGlut.GFP} P{VGlut-GAL4.D}
Genes (4)
	dlg1 Mmus\Cd8a Scer\GAL4 VGlut
Insertions (1)
	P{GAL4}BG380