| Autor: |
Purro, Silvia A., Dickins, Ellen M., Salinas, Patricia C. |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 3/7/2012, Vol. 32 Issue 10, p3492-3498, 7p |
| Abstrakt: |
Extensive evidence supports a central role for amyloid-&BGR; (A&BGR;) in the pathogenesis of Alzheimer's disease (AD). Synaptic loss mediated by A&BGR;in early stages of the disease might contribute to cognitive impairments. However, little is known about the mechanism by which A&bgr; induces the loss of synapses. The expression of the Wnt antagonist Dickkopf-1 (Dkk1) is increased in brains of AD patients and in AD transgenic mouse models, suggesting that dysfunction of Wnt signaling could contribute to AD pathology. Here we report that acute exposure to A&BGR;oligomers induces Dkk1 expression together with the loss of synaptic sites. Importantly, Dkk1-neutralizing antibodies suppress A&BGR;-induced synapse loss in mouse brain slices. In mature rat hippocampal neurons, Dkk1 decreases the number of synapses without affecting cell viability. Ultrastructural analyses revealed that Wnt blockade decreases the size of presynaptic and postsynaptic terminals. Time-lapse recordings of RFP-labeled stable synaptic sites demonstrate that Dkk1 induces the dispersal of synaptic components. These findings identify Dkk1 as a potential therapeutic target for the treatment of AD. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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