Glycogen synthase kinase‐3 inhibition is integral to long‐term potentiation

Hooper, Claudie; Маркевич, В. С.; Plattner, Florian; Killick, Richard; Schofield, Emma; Engel, Tobías; Hernández, Félix; Anderton, Brian H.; Rosenblum, Kobi; Bliss, T. V. P.; Cooke, Sam; Ávila, Jesús; Lucas, José J.; Giese, K. Peter; Stephenson, John; Lovestone, Simon

doi:10.1111/j.1460-9568.2006.05245.x

Cited by 308 publications

(270 citation statements)

References 38 publications

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“…6 A). To further confirm the changes of these postsynaptic proteins, we prepared the P2 fraction to enrich the synaptic associated proteins (Hooper et al, 2007). We found that the levels of NR2A/B subunits were also reduced in addition to a more prominent decrease of PSD93 after wortmannin treatment, and these proteins were partially restored when GSK-3 was si- Figure 3.…”

Section: Upregulation Of Gsk-3 Reduces the Level Of Psd93 And Nr2a/bmentioning

confidence: 99%

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Activation of Glycogen Synthase Kinase-3 Inhibits Long-Term Potentiation with Synapse-Associated Impairments

Zhu

Wang²,

Liú³

et al. 2007

J. Neurosci.

214

165

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Activation of glycogen synthase kinase-3 (GSK-3) can cause memory deficits as seen in Alzheimer's disease, the most common ageassociated dementia, but the mechanism is not understood. Here, we found that activation of GSK-3 by wortmannin or transient overexpression of wild-type GSK-3␤ could suppress the induction of long-term potentiation (LTP) in rat hippocampus, whereas simultaneous inhibition of GSK-3 by lithium or SB216763 or transient expression of a dominant-negative GSK-3␤ mutant (dnGSK-3␤) preserved the LTP. After high-frequency stimulation (HFS), the presynaptic release of glutamate and the expression/clustering of synapsin I, a synaptic vesicle protein playing an important role in neurotransmitter release, decreased markedly after upregulation of GSK-3. In vitro studies further demonstrated that GSK-3 inhibited the expression of SynI independent of HFS. In postsynaptic level, the expression of PSD93 and NR2A/B proteins decreased significantly when GSK-3 was activated. The LTP-associated synapse impairments including less presynaptic active zone, thinner postsynaptic density, and broader synaptic cleft were also prominent in the hippocampal slices after HFS with activation of GSK-3. These synaptic impairments were attenuated when GSK-3 was simultaneously inhibited by LiCl or SB216763 or transient expression of dnGSK-3. We conclude that upregulation of GSK-3 impairs the synaptic plasticity both functionally and structurally, which may underlie the GSK-3-involved memory deficits.

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Section: Upregulation Of Gsk-3 Reduces the Level Of Psd93 And Nr2a/bmentioning

confidence: 99%

“…A most recent study demonstrated that GSK-3 was inhibited during LTP, and it was activated during long-term depression (Peineau et al, 2007). Another recent study showed that conditional expression of GSK-3 in mouse brain inhibited LTP (Hooper et al, 2007). Until now, the possible molecular link between GSK-3 and LTP is still missing.…”

Section: Introductionmentioning

confidence: 99%

Activation of Glycogen Synthase Kinase-3 Inhibits Long-Term Potentiation with Synapse-Associated Impairments

Zhu

Wang²,

Liú³

et al. 2007

J. Neurosci.

214

165

View full text Add to dashboard Cite

show abstract

“…Inhibition of GSK-3b during LTP has been hypothesized to prevent early subsequent LTD (Peineau et al 2007). Accordingly, LTP induction is associated with inhibition of GSK-3b (Hooper et al 2007). Inhibitory S9 phosphorylation of GSK-3b increases in hippocampus and amygdala during fear LTM formation (Fujio et al 2007;Maguschak et al 2008).…”

Section: Pi3kmentioning

confidence: 99%

The roles of protein kinases in learning and memory

2013

Self Cite

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In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate gene expression and protein synthesis causing structural changes at existing synapses as well as synaptogenesis. Here, we review the roles of these kinases in short-term memory formation, memory consolidation, memory storage, retrieval, reconsolidation, and extinction. Specifically, we discuss the roles of calcium/calmodulin-dependent kinase II (CaMKII

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“…Furthermore, in the FTDP-17 model animal, Li + , which inhibits GSK-3β, prevented NFT formation (16,37). Overexpression of GSK-3β in mouse induces tau hyperphosphorylation and a decline in cognitive performance accompanied with inhibition of LTP (20,33). This decline in cognitive performance is due to impairment of learning.…”

Section: Activation Of Gsk-3β During Aging Brainmentioning

confidence: 99%

“…Activation of GSK-3β is required for LTD but inhibits LTP (33). The inhibition of LTP by activation of GSK-3β impaired learning ability.…”

Section: Regulation Of Synaptic Function By Gsk-3βmentioning

confidence: 99%

Drug Development Targeting the Glycogen Synthase Kinase-3β (GSK-3β)-Mediated Signal Transduction Pathway: Role of GSK-3β in Adult Brain

Takashima

2009

J Pharmacol Sci

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Abstract. Glycogen synthase kinase-3β (GSK-3β) is a constitutively active kinase. Since its activation results in neurofibrillary tangle (NFT) deposits in aged and Alzheimer's disease (AD) brains, GSK-3β may be inhibited under normal conditions but activated under pathological conditions. Given its link to NFT formation, we sought to determine whether GSK-3β exists in the brain as a "pathological time bomb" that promotes disease development. To address this hypothesis, we analyzed GSK-3β heterozygote (GSK+/ −) mice, which express GSK-3β at 50% wild-type levels. When tested in the Morris water maze test, GSK+/ − mice surprisingly exhibited retrograde amnesia. Further analysis indicated that GSK+/ − mice had impaired memory reconsolidation but normal memory consolidation. Therefore, we concluded that GSK-3β activation is required for memory reconsolidation in the adult brain.

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Glycogen synthase kinase‐3 inhibition is integral to long‐term potentiation

Cited by 308 publications

References 38 publications

Activation of Glycogen Synthase Kinase-3 Inhibits Long-Term Potentiation with Synapse-Associated Impairments

Activation of Glycogen Synthase Kinase-3 Inhibits Long-Term Potentiation with Synapse-Associated Impairments

The roles of protein kinases in learning and memory

Drug Development Targeting the Glycogen Synthase Kinase-3β (GSK-3β)-Mediated Signal Transduction Pathway: Role of GSK-3β in Adult Brain

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