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- Title
Glycogen synthase kinase-3 inhibition is integral to long-term potentiation.
- Authors
Hooper, Claudie; Markevich, Vladimir; Plattner, Florian; Killick, Richard; Schofield, Emma; Engel, Tobias; Hernandez, Felix; Anderton, Brian; Rosenblum, Kobi; Bliss, Tim; Cooke, Sam F.; Avila, Jesús; Lucas, José J.; Giese, Karl Peter; Stephenson, John; Lovestone, Simon
- Abstract
Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase regulating diverse cellular functions including metabolism, transcription and cell survival. Numerous intracellular signalling pathways converge on GSK-3 and regulate its activity via inhibitory serine-phosphorylation. Recently, GSK-3 has been involved in learning and memory and in neurodegeneration. Here, we present evidence that implicates GSK-3 in synaptic plasticity. We show that phosphorylation at the inhibitory Ser9 site on GSK-3β is increased upon induction of long-term potentiation (LTP) in both hippocampal subregions CA1 and the dentate gyrus (DG) in vivo. The increase in inhibitory GSK-3β phosphorylation is robust and persists for at least one hour postinduction. Furthermore, we find that LTP is impaired in transgenic mice conditionally overexpressing GSK-3β. The LTP deficits can be attenuated/rescued by chronic treatment with lithium, a GSK-3 inhibitor. These results suggest that the inhibition of GSK-3 facilitates the induction of LTP and this might explain some of the negative effects of GSK-3 on learning and memory. It follows that this role of GSK-3β in LTP might underlie some of the cognitive dysfunction in diseases where GSK-3 dysfunction has been implicated, including Alzheimer's and other dementias.
- Subjects
GLYCOGEN synthase kinase-3; SERINE; PHOSPHORYLATION; NEUROPLASTICITY; WNT proteins; NOTCH genes; ALZHEIMER'S disease
- Publication
European Journal of Neuroscience, 2007, Vol 25, Issue 1, p81
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2006.05245.x