Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory

Kelleher, Raymond J.; Govindarajan, Arvind; Jung, Hae‐Yoon; Kang, H. Chuan; Tonegawa, Susumu

doi:10.1016/s0092-8674(04)00115-1

Cited by 764 publications

(678 citation statements)

References 53 publications

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“…Therefore, PGS32 presumably was able to prime the ERK/MAP kinase cascade by activating ERK. A large body of research has demonstrated that ERK activation is required for the induction and maintenance of LTP, as well as for hippocampal memory formation and retention [26,27] . The ability of PGS32 to activate ERK therefore provides initial evidence that this saponin can play a role in regulating cognitive function and synaptic transmission.…”

Section: Discussionmentioning

confidence: 99%

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

Xue

Yuan

et al. 2009

Acta Pharmacol Sin

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Aim: The aim of this study was to investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (polygalasaponin XXXII, PGS32) isolated from the roots of Polygala tenuifolia Willd. Methods: The Morris water maze was used to evaluate the spatial learning and memory of mice. To detect the basic properties of synaptic transmission and long-term potentiation (LTP) in the dentate gyrus of rats, electrophysiological recordings were made of evoked potentials. Western blotting analysis and immunofluorescence assays were used to determine the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), synapsin I and the expression of brain derived neurotrophic factor (BDNF). Results: When administered at 0.125, 0.5, or 2 mg/kg, PGS32 could significantly prevent scopolamine-induced cognitive impairments in mice. Intracerebroventricular (icv) administration of PGS32 greatly enhanced basic synaptic transmission in the dentate gyrus of rats and induced LTP. In primary hippocampal neurons, as well as in the hippocampus of maze-trained mice, PGS32 activated the mitogen-activated protein (MAP) kinase cascade by promoting phosphorylation of ERK, CREB and synapsin I. The expression of BDNF was also greatly enhanced in the hippocampus. Conclusion: Our findings suggest that PGS32 can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade and enhancement of the level of BDNF. Therefore, PGS32 shows promise as a potential cognition-enhancing therapeutic drug.

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Section: Discussionmentioning

confidence: 99%

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

Xue

Yuan

et al. 2009

Acta Pharmacol Sin

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“…Another ADR, mycalolide B, also blocked the effect of activin on spine length, and the average spine lengths in neurons treated with activin alone versus neurons treated with activin and 50 nM mycalolide B were 1.59±0.054 m versus 1.50±0.049 m, respectively. The MAP kinase pathway is involved in the effects of activin Because MAP kinase signaling modulates dendritic spine morphology (Wu et al, 2001) and LTP maintenance (Kelleher, 3rd et al, 2004;Patterson et al, 2001), we asked whether the MAP kinase pathway also mediates the activin signaling that alters spinal morphology. When hippocampal primary cultures were treated with activin, phosphorylation of ERK1/2 increased by twofold within 0.5-1 hour (Fig.…”

Section: F-actin-destabilizing Reagents Block the Effects Of Activinmentioning

confidence: 99%

Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics

Shoji-Kasai

Ageta

Hasegawa

et al. 2007

Journal of Cell Science

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Long-lasting modifications in synaptic transmission depend on de novo gene expression in neurons. The expression of activin, a member of the transforming growth factor β (TGF-β) superfamily, is upregulated during hippocampal long-term potentiation (LTP). Here, we show that activin increased the average number of presynaptic contacts on dendritic spines by increasing the population of spines that were contacted by multiple presynaptic terminals in cultured neurons. Activin also induced spine lengthening, primarily by elongating the neck, resulting in longer mushroom-shaped spines. The number of spines and spine head size were not significantly affected by activin treatment. The effects of activin on spinal filamentous actin (F-actin) morphology were independent of protein and RNA synthesis. Inhibition of cytoskeletal actin dynamics or of the mitogen-activated protein (MAP) kinase pathway blocked not only the activin-induced increase in the number of terminals contacting a spine but also the activin-induced lengthening of spines. These results strongly suggest that activin increases the number of synaptic contacts by modulating actin dynamics in spines, a process that might contribute to the establishment of late-phase LTP.

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“…Kelleher et al (2004) demonstrated that the extracellular signalregulated kinase (ERK)/mitogen-activated protein kinase pathway is involved in regulating the phosphorylation state of numerous factors implicated in controlling translation initiation, including eIF4E, 4E-BP1, and the ribosomal protein S6. The genetically altered mice used in this study also showed deficits in long-term potentiation (LTP) and hippocampus-dependent memory.…”

Section: Introductionmentioning

confidence: 99%

Translational Control via the Mammalian Target of Rapamycin Pathway Is Critical for the Formation and Stability of Long-Term Fear Memory in Amygdala Neurons

Parsons¹,

Gafford²,

Helmstetter³

2006

J. Neurosci.

223

177

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The mammalian target of rapamycin kinase (mTOR) regulates protein synthesis in neurons at the translational level through phosphorylation of several intracellular targets. Recent work in invertebrates indicates that mTOR-dependent translational control may be critical for the induction and maintenance of activity-dependent synaptic plasticity underlying memory formation. Here, we report that training rats in a simple fear conditioning procedure evokes a time-dependent increase in the phosphorylation of p70s6 kinase, a major direct downstream target of mTOR. When the activation of mTOR was prevented by posttraining injection of rapamycin into the amygdala, formation of the memory and the increase in p70s6 kinase phosphorylation was attenuated. Furthermore, when rapamycin was applied to the amygdala after the recall of a previously stored fear memory, subsequent retention was disrupted, indicating that local translational control at active synapses is required for the stability as well as the formation of long-term memory in this system.

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Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory

Cited by 764 publications

References 53 publications

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory

Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics

Translational Control via the Mammalian Target of Rapamycin Pathway Is Critical for the Formation and Stability of Long-Term Fear Memory in Amygdala Neurons

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