Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures

Wang, Baohui; Hou, Qun; Lu, Yu-Qiang; Jia, Mengmeng; Qiu, Tao; Wang, Xiao-Hang; Zhang, Zhengxiang; Jiang, Yan

doi:10.1016/j.brainres.2017.10.009

Cited by 58 publications

(40 citation statements)

References 39 publications

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“…KD alleviates seizure severity while decreasing the number of apoptotic cells and the number of damaged mitochondria in the hippocampi of kindled rats. These effects correlate with autophagy activation as evidenced by an increase of hippocampal Beclin-1, ATG5, and LC3-II/ LC3-I ratio along with a decrease of the autophagy substrate p62 compared with PTZ-kindled rats which are fed with normal diet [133]. Remarkably, these effects are abolished by pretreatment with the autophagy inhibitor 3-MA, while rapamycin pretreatment protects from neuronal cell death in the hippocampus despite not affecting seizure severity.…”

Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 88%

“…Autophagy activation is also detected following ibuprofen administration in PTZ-treated rats, which is associated with reduced seizure number, duration, and severity, along with decreased astrogliosis and astrocyte proliferation [132]. Likewise, autophagy is implicated in the beneficial effects of the ketogenic diet (KD) in PTZ-kindled rats [133]. KD alleviates seizure severity while decreasing the number of apoptotic cells and the number of damaged mitochondria in the hippocampi of kindled rats.…”

Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 99%

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mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

Limanaqi

Biagioni

Busceti

et al. 2020

IJMS

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Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression is sufficient to induce epilepsy in experimental models, while rescuing autophagy prevents epileptogenesis, improves behavioral alterations, and provides neuroprotection in seizure-induced neuronal damage. The implication of autophagy in epileptogenesis and maturation phenomena related to seizure activity is supported by evidence indicating that autophagy is involved in the molecular mechanisms which are implicated in epilepsy. In general, mTOR-dependent autophagy regulates the proliferation and migration of inter-/neuronal cortical progenitors, synapse development, vesicular release, synaptic plasticity, and importantly, synaptic clustering of GABAA receptors and subsequent excitatory/inhibitory balance in the brain. Similar to autophagy, the ubiquitin–proteasome system is regulated downstream of mTOR, and it is implicated in epileptogenesis. Thus, mTOR-dependent cell-clearing systems are now taking center stage in the field of epilepsy. In the present review, we discuss such evidence in a variety of seizure-related disorders and models. This is expected to provide a deeper insight into the molecular mechanisms underlying seizure activity.

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Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 88%

Section: Pentylenetetrazole (Ptz)-induced Seizuresmentioning

confidence: 99%

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

Limanaqi

Biagioni

Busceti

et al. 2020

IJMS

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“…Interestingly, feeding mice a ketogenic diet inhibits MTORC1 activity in the liver (Roberts et al, 2017) and in the small bowel mucosa , which might lead to autophagy induction in the intestine, knowing that this is important for longevity in model organisms (Gelino et al, 2016). Ketogenic diet also induces autophagy in the hippocampus (Wang et al, 2018), increases energy expenditure and respiratory exchange rates, and improves blood lipid profiles in several distinct mouse strains (Barrington et al, 2018).…”

Section: Author Manuscriptmentioning

confidence: 99%

Carbotoxicity-noxious effects of carbohydrates

Kroemer¹,

Lopez-Otin²,

Madeo³

et al. 2019

ESPE

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Modern nutrition is often characterized by the excessive intake of different types of carbohydrates ranging from digestible polysaccharides to refined sugars that collectively mediate noxious effects on human health, a phenomenon that we refer to as ''carbotoxicity.'' Epidemiological and experimental evidence combined with clinical intervention trials underscore the negative impact of excessive carbohydrate uptake, as well as the beneficial effects of reducing carbs in the diet. We discuss the molecular, cellular, and neuroendocrine mechanisms that link exaggerated carbohydrate intake to disease and accelerated aging as we outline dietary and pharmacologic strategies to combat carbotoxicity.Qualitative nutritional cues play a major role in determining physical shape and fitness. This applies to micronutrients that may have positive effects on human health (such as the minimally required doses of vitamins and other micronutrients including oligoelements and polyamines) (Madeo et al., 2018) or toxic effects, as demonstrated for trans-unsaturated fattyThe second major change in carbohydrate uptake is marked by the mass production and consumption of refined sugars. The history of sugar is intimately linked to the laborintensive cultivation and extraction of sugarcane, first in tropical Southeast Asia, later in the Kroemer et al.

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“…In contrast, once the destruction of cellular DNA occurs, it is usually not considered to be completely reversible (59). Apoptosis in the nervous system can be involved in retinal degeneration (24, 76), pain sensitivity and neuronal injury (77), Aβ injury (13, 78–82), epilepsy (83, 84), Parkinson’s disease (11, 41, 85–87), diabetic injury (14, 17, 26, 88–90), traumatic brain injury (41, 91–93), and autism (94). …”

Section: Autophagy and Apoptosismentioning

confidence: 99%

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Maiese¹

2018

CNR

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BACKGROUND With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs). RESULTS Circadian clock genes, non-coding RNAs, and FoxOs offer exciting prospects to potentially limit or remove the significant disability and death associated with neurodegenerative disorders. Each of these pathways have an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease such as atherosclerosis. FoxOs provide exciting prospects to block neuronal apoptotic death and to activate pathways of autophagy to remove toxic accumulations in neurons that can lead to neurodegenerative disorders. CONCLUSIONS Continued work with circadian clock genes, non-coding RNAs, and FoxOs can offer new prospects and hope for the development of vital strategies for the treatment of neurodegenerative diseases. These innovative investigative avenues have the potential to significantly limit disability and death from these devastating disorders.

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Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures

Cited by 58 publications

References 39 publications

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update

Carbotoxicity-noxious effects of carbohydrates

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

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