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Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice
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Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice
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Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice
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Journal Article
Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice
2014
Overview
Synapse degeneration is an early and invariant feature of neurodegenerative diseases. Indeed, synapse loss occurs prior to neuronal degeneration and correlates with the symptom severity of these diseases. However, the molecular mechanisms that trigger synaptic loss remain poorly understood. Here we demonstrate that deficient Wnt signalling elicits synaptic degeneration in the adult striatum. Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine receptor clusters. Synapse loss occurs in the absence of axon retraction or cell death. The remaining excitatory terminals contain fewer synaptic vesicles and have a reduced probability of evoked transmitter release. IDkk1 mice show impaired motor coordination and are irresponsive to amphetamine. These studies identify Wnts as key endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases.
Synapse degeneration is an early feature of neurodegenerative diseases. Here the authors show that Wnts are endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
/ 13/2
/ 13/51
/ 14/19
/ 14/28
/ 14/63
/ 64/60
/ 82/29
/ 82/80
/ Animals
/ Dopamine
/ Female
/ Humanities and Social Sciences
/ Intercellular Signaling Peptides and Proteins - metabolism
/ Male
/ Mice
/ Neurodegenerative Diseases - metabolism
/ Neurodegenerative Diseases - physiopathology
/ Receptors, Dopamine D1 - metabolism
/ Receptors, Dopamine D2 - metabolism
/ Science
