Dataset Information

HFS-Triggered AMPK Activation Phosphorylates GSK3β and Induces E-LTP in Rat Hippocampus In Vivo.

ABSTRACT:

Background

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy and nutrient status, with substantial amount of cross talk with other signaling pathways, including its phosphorylation by Akt, PKA, and GSK3β.

Aims

Various signaling pathways and energy-consuming transport of glutamate receptors subunits are required in synaptic plasticity. However, it is unknown which energy sensors integrate the signaling pathways in these processes. In this article, we elucidated the role of AMPK activation and GSK3β phosphorylation after HFS during the inducement of early-phase long-term potentiation (E-LTP).

Methods

Synaptic LTP in vivo was induced by high-frequency stimulation (HFS at 200 Hz at a 5-s interval). In addition, phosphorylation of AMPK and glycogen synthase kinase 3β (GSK3β) were measured using Western blotting. The amount of hippocampal AMP, ADP and ATP was measured by HPLC.

Results

We showed that the phosphorylation of AMPK and GSK3β was significantly increased by HFS in vivo. HFS-induced AMPK activation occurred via increased (AMP + ADP)/ATP ratio and activation of Ca(2+) /calmodulin-dependent kinase kinase beta (CaMKKβ). Pharmacological inhibition of AMPK by compound C (CC) prevented HFS-induced inhibitory phosphorylation of GSK3β and the induction of LTP in dentate gyrus (DG) area in vivo.

Conclusions

Our findings reveal that HFS-triggered AMPK activation phosphorylates GSK3β and induces E-LTP in vivo.

SUBMITTER: Yu DF

PROVIDER: S-EPMC6492836 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

HFS-Triggered AMPK Activation Phosphorylates GSK3β and Induces E-LTP in Rat Hippocampus In Vivo.

Yu Dan-Fang DF Shen Zu-Cheng ZC Wu Peng-Fei PF Guan Xin-Lei XL Chen Tao T Jin You Y Hu Zhuang-Li ZL Ni Lan L Wang Fang F Chen Jian-Guo JG Long Li-Hong LH

CNS neuroscience & therapeutics 20160325 6

<h4>Background</h4>The AMP-activated protein kinase (AMPK) is a sensor of cellular energy and nutrient status, with substantial amount of cross talk with other signaling pathways, including its phosphorylation by Akt, PKA, and GSK3β.<h4>Aims</h4>Various signaling pathways and energy-consuming transport of glutamate receptors subunits are required in synaptic plasticity. However, it is unknown which energy sensors integrate the signaling pathways in these processes. In this article, we elucidated ...[more]

PMID: 27012879

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Project description:Transcranial focused ultrasound (tFUS) neuromodulation provides a promising emerging non-invasive therapy for the treatment of neurological disorders. Many studies have demonstrated the ability of tFUS to elicit transient changes in neural responses. However, the ability of tFUS to induce sustained changes need to be carefully examined. In this study, we use the long-term potentiation/long term depression (LTP/LTD) model in the rat hippocampus, the medial perforant path (mPP) to dentate gyrus (DG) pathway, to explore whether tFUS is capable of encoding frequency specific information to induce plasticity. Single-element focused transducers were used for tFUS stimulation with ultrasound fundamental frequency of 0.5 MHz and nominal focal distance of 38 mm tFUS stimulation is directed to mPP. Measurement of synaptic connectivity is achieved through the slope of field excitatory post synaptic potentials (fEPSPs), which are elicited using bipolar electrical stimulation electrodes and recorded at DG using extracellular electrodes to quantify degree of plasticity. We applied pulsed tFUS stimulation with total duration of 5 min, with 5 levels of pulse repetition frequencies each administered at 50 Hz sonication frequency at the mPP. Baseline fEPSP is recorded 10 min prior, and 30+ minutes after tFUS administration. In N = 16 adult wildtype rats, we observed sustained depression of fEPSP slope after 5 min of tFUS focused at the presynaptic field mPP. Across all PRFs, no significant difference in maximum fEPSP slope change was observed, average tFUS induced depression level was observed at 19.6%. When compared to low frequency electrical stimulation (LFS) of 1 Hz delivered to the mPP, the sustained changes induced by tFUS stimulation show no statistical difference to LFS for up to 24 min after tFUS stimulation. When both the maximum depression effects and the duration of sustained effects are both taken into account, PRF 3 kHz can induce significantly larger effects than other PRFs tested. tFUS stimulation is measured with a spatial-peak pressure amplitude of 99 kPa, translating to an estimation of 0.43 °C temperature increase when assuming no loss of heat. The results suggest the ability of tFUS to encode sustained changes in synaptic connectivity through mechanism which are unlikely to involve thermal changes.

Dataset Information

HFS-Triggered AMPK Activation Phosphorylates GSK3β and Induces E-LTP in Rat Hippocampus In Vivo.

Background

Aims

Methods

Results

Conclusions

Publications

HFS-Triggered AMPK Activation Phosphorylates GSK3β and Induces E-LTP in Rat Hippocampus In Vivo.

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