Electroconvulsive seizure inhibits the mTOR signaling pathway via AMPK in the rat frontal cortex

Kim, Se Hyun; Yu, Hyun Sook; Huh, Seonghoo; Kang, Ung Gu; Kim, Yong Sik

doi:10.1007/s00213-021-06015-2

Cited by 12 publications

(8 citation statements)

References 73 publications

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“…We have reported that repeated ECS treatments for 10 days in rats induces autophagy via the activation of AMPK-ULK1-Beclin1 signaling 26 and AMPK-mediated mTOR inhibition 27 in the frontal cortex. AMPK plays a critical role in the autophagy process.…”

Section: Discussionmentioning

confidence: 99%

“…26 Our previous study found that the ECS treatments increased the phosphorylation of Raptor, which is another substrate of AMPK and known to suppress mTOR activity, 46 and decreased the phosphorylation of p70S6K and S6, the downstream molecules of mTOR1. 27 To investigate those autophagy-relevant signaling changes by ECS in MPTP PD mouse model, we established our ECS protocol for mouse, 3 times per week for 2 weeks, in a trialand-error manner, but that is very similar to the ECT protocol used in the actual human treatment. In the present study, we observed comparable results with the rat model.…”

Section: Discussionmentioning

confidence: 99%

“…25 Moreover, our recent studies reported that repeated ECS treatments induced autophagy activation and more autophagosome formations in the rat frontal cortex via AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling pathway. 26,27 Autophagy impairments in the neurodegenerative disorders such as PD and Alzheimer disease have been increasingly given attention, and autophagy manipulation is currently highlighted as a novel treatment strategy for the diseases. 28,29 Here, we demonstrated that repeated ECS treatments normalized motor deficits in the MPTP PD mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model

Huh

Kang

et al. 2023

Psychiatry Investig

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Objective Electroconvulsive seizure (ECS) is a potent treatment modality for various neuropsychiatric diseases, including Parkinson disease (PD). Recent animal studies showed that repeated ECS activates autophagy signaling, the impairment of which is known to be involved in PD. However, the effectiveness of ECS on PD and its therapeutic mechanisms have not yet been investigated in detail.Methods Systemic injection of a neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), which destroys dopaminergic neurons in the substantia nigra compacta (SNc), in mice was utilized to induce an animal model of PD. Mice were treated with ECS 3 times per week for 2 weeks. Behavioral changes were measured with a rotarod test. Molecular changes related to autophagy signaling in midbrain including SNc, striatum, and prefrontal cortex were analyzed with immunohistochemistry and immunoblot analyses.Results Repeated ECS treatments normalized the motor deficits and the loss of dopamiergic neurons in SNc of the MPTP PD mouse model. In the mouse model, LC3-II, an autophagy marker, was increased in midbrain while decreased in prefrontal cortex, both of which were reversed by repeated ECS treatments. In the prefrontal cortex, ECS-induced LC3-II increase was accompanied with AMP-activated protein kinase (AMPK)-Unc-51-like kinase 1-Beclin1 pathway activation and inhibition of mamalian target of rapamycin signaling which promotes autophagy initiation.Conclusion The findings revealed the therapeutic effects of repeated ECS treatments on PD, which could be attributed to the neuroprotective effect of ECS mediated by AMPK-autophagy signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model

Huh

Kang

et al. 2023

Psychiatry Investig

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“…mTOR can modulate insulin physiology in neurodegenerative studies to increase survival of astrocytes [429], block hyperglycemic endothelial cell injury [430], and preserve metabolic regulation [431]. As a component of the mTOR pathway, the AMP-activated protein kinase (AMPK) modulates cellular metabolism [106,169,198,237,378,381,382,394,432,433], and the activation of AMPK reduces cognitive loss in studies of DM and AD [434,435], removes cerebral Aβ [436] and tau [437], limits Aβ neurotoxicity [392], diminishes long-term inflammation in in the nervous system [10,71,438,439], and fosters pathways for healthy aging [6,440,441].…”

Section: The Mechanistic Target Of Rapamycin and Multiple Sclerosismentioning

confidence: 99%

Cognitive Impairment in Multiple Sclerosis

Maiese

2023

Bioengineering

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Almost three million individuals suffer from multiple sclerosis (MS) throughout the world, a demyelinating disease in the nervous system with increased prevalence over the last five decades, and is now being recognized as one significant etiology of cognitive loss and dementia. Presently, disease modifying therapies can limit the rate of relapse and potentially reduce brain volume loss in patients with MS, but unfortunately cannot prevent disease progression or the onset of cognitive disability. Innovative strategies are therefore required to address areas of inflammation, immune cell activation, and cell survival that involve novel pathways of programmed cell death, mammalian forkhead transcription factors (FoxOs), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and associated pathways with the apolipoprotein E (APOE-ε4) gene and severe acute respiratory syndrome coronavirus (SARS-CoV-2). These pathways are intertwined at multiple levels and can involve metabolic oversight with cellular metabolism dependent upon nicotinamide adenine dinucleotide (NAD+). Insight into the mechanisms of these pathways can provide new avenues of discovery for the therapeutic treatment of dementia and loss in cognition that occurs during MS.

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“…In addition, nicotinamide relies upon AMPK to preserve mitochondria function [261], and Wnt family members employ AMPK to limit neuronal injury [498]. AMPK can maintain electrical activity of the cortex for behavior control [499], AMPK oversees endothelial tight junctions [500], and AMPK can promote mitochondrial integrity during ferroptotic cell death [169]. In the absence of AMPK activity, cell senescence, cell death, and mitochondrial injury can ensue [3,137].…”

Section: Wnt Signaling and Wisp1 Oversight In Diabetes Mellitus And M...mentioning

confidence: 99%

Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

Maiese

2023

Cells

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Metabolic disorders and diabetes (DM) impact more than five hundred million individuals throughout the world and are insidious in onset, chronic in nature, and yield significant disability and death. Current therapies that address nutritional status, weight management, and pharmacological options may delay disability but cannot alter disease course or functional organ loss, such as dementia and degeneration of systemic bodily functions. Underlying these challenges are the onset of aging disorders associated with increased lifespan, telomere dysfunction, and oxidative stress generation that lead to multi-system dysfunction. These significant hurdles point to the urgent need to address underlying disease mechanisms with innovative applications. New treatment strategies involve non-coding RNA pathways with microRNAs (miRNAs) and circular ribonucleic acids (circRNAs), Wnt signaling, and Wnt1 inducible signaling pathway protein 1 (WISP1) that are dependent upon programmed cell death pathways, cellular metabolic pathways with AMP-activated protein kinase (AMPK) and nicotinamide, and growth factor applications. Non-coding RNAs, Wnt signaling, and AMPK are cornerstone mechanisms for overseeing complex metabolic pathways that offer innovative treatment avenues for metabolic disease and DM but will necessitate continued appreciation of the ability of each of these cellular mechanisms to independently and in unison influence clinical outcome.

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Electroconvulsive seizure inhibits the mTOR signaling pathway via AMPK in the rat frontal cortex

Cited by 12 publications

References 73 publications

Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model

Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model

Cognitive Impairment in Multiple Sclerosis

Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

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