Absolute requirement of GDNF for adult catecholaminergic neuron survival

被引：265

作者：

Pascual, Alberto ^{[1
]}

Hidalgo-Figueroa, Maria ^{[1
]}

Piruat, Jose I. ^{[1
]}

Pintado, C. Oscar ^{[1
]}

Gomez-Diaz, Raquel ^{[1
]}

Lopez-Barneo, Jose ^{[1
]}

机构：

[1] Univ Seville, Hosp Univ Virgen Rocio, Inst Biomed Sevilla, Consejo Super Invest Cient, Seville 41013, Spain

来源：

NATURE NEUROSCIENCE | 2008年 / 11卷 / 07期

关键词：

D O I：

10.1038/nn.2136

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

GDNF 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.

引用

页码：755 / 761

页数：7

共 44 条

[41]

Trupp M, 1997, J NEUROSCI, V17, P3554

[42] Selective glial cell line-derived neurotrophic factor production in adult dopaminergic carotid body cells in situ and after intrastriatal transplantation [J].