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Absolute requirement of GDNF for adult catecholaminergic neuron survival

AuthorsPascual Bravo, Alberto ; Hidalgo Figueroa, María; Piruat, José I.; Pintado, C. Oscar; Gómez-Díaz, Raquel; López-Barneo, José
KeywordsEndogenous GDNF
Conditional gene deletion
Dopaminergic cell death
Noradrenergic neuronal death
Parkinson's disease
Mouse model
Issue Date8-Jun-2008
PublisherNature Publishing Group
CitationNature Neuroscience 11: 755-761 (2008)
AbstractGDNF is a potent neurotrophic factor that protects catecholaminergic neurons from toxic damage and induces fiber outgrowth. However, the actual role of endogenous GDNF in the normal adult brain is unknown, even though GDNF-based therapies are considered promising for neurodegenerative disorders. We have generated a conditional GDNF-null mouse to suppress GDNF expression in adulthood, hence avoiding the developmental compensatory modifications masking its true physiologic action. After Gdnf ablation, mice showed a progressive hypokinesia and a selective decrease of brain tyrosine hydroxylase (Th) mRNA, accompanied by pronounced catecholaminergic cell death, affecting most notably the locus coeruleus, which practically disappears; the substantia nigra; and the ventral tegmental area. These data unequivocally demonstrate that GDNF is indispensable for adult catecholaminergic neuron survival and also show that, under physiologic conditions, downregulation of a single trophic factor can produce massive neuronal death.
Description33 páginas, 7 figuras, 1 tabla.
Publisher version (URL)http://dx.doi.org/10.1038/nn.2136
Appears in Collections:(IBIS) Artículos
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