Abstract：
:Age-related decreases in neural function result in part from alterations in synapses. To identify molecular defects that lead to such changes, we focused on the outer retina, in which synapses are markedly altered in old rodents and humans. We found that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate this process. In old mice, synaptic remodeling was accompanied by specific decreases in the levels of total LKB1 and active (phosphorylated) AMPK. In the absence of either kinase, young adult mice developed retinal defects similar to those that occurred in old wild-type animals. LKB1 and AMPK function in rod photoreceptors where their loss leads to aberrant axonal retraction, the extension of postsynaptic dendrites and the formation of ectopic synapses. Conversely, increasing AMPK activity genetically or pharmacologically attenuates and may reverse age-related synaptic alterations. Together, these results identify molecular determinants of age-related synaptic remodeling and suggest strategies for attenuating these changes.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Samuel MA,Voinescu PE,Lilley BN,de Cabo R,Foretz M,Viollet B,Pawlyk B,Sandberg MA,Vavvas DG,Sanes JRdoi
10.1038/nn.3772subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1190-7issue
9eissn
1097-6256issn
1546-1726pii
nn.3772journal_volume
17pub_type
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