Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis

Jeong, Jae Hoon; Yu, Kwang Sik; Bak, Dong Ho; Lee, Je‐Hun; Lee, Nam Seob; Jeong, Young‐Gil; Kim, Dong Kwan; Kim, Jwa‐Jin; Han, Seung‐Yun

doi:10.3892/etm.2016.3852

Cited by 37 publications

(22 citation statements)

References 34 publications

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“…Several studies have demonstrated a neuroprotective role for autophagy in acute hypoxic/ischaemic brain injury 26 , 27 . Hypoxia caused by compromised blood supply results in phosphorylation and activation of AMPK, which can also suppress phosphorylation of mTOR, can directly or indirectly promote autophagy induction.…”

Section: Discussionmentioning

confidence: 99%

Involvement of impaired autophagy and mitophagy in Neuro-2a cell damage under hypoxic and/or high-glucose conditions

Song

Zou

et al. 2018

Sci Rep

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Chronic cerebral hypoperfusion (CCH) plays an insidious role in the development of cognitive impairment. Considerable evidence suggests that Diabetes Mellitus (DM) as a vascular risk factor may exacerbate CCH and is closely related to cognitive decline. Dysregulation of autophagy is known to be associated with the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease. To elucidate the role of autophagy in CCH- and/or DM-related pathogenesis, mouse neuroblastoma Neuro-2a cells were exposed to hypoxia and/or high glucose for 48 h, mimicking CCH complicated with DM pathologies. Chronic hypoxia reduced cell proliferation and increased levels of cleaved caspase-3, whereas high glucose had no obvious synergistic toxic effect. Accumulation of autophagic vacuoles under hypoxia may be due to both autophagy impairment and induction, with the former accounting for Neuro-2a cell death. Additionally, aberrant accumulation of mitochondria in Neuro-2a cells may be attributed to insufficient BNIP3-mediated mitophagy due to poor interaction between BNIP3 and LC3-II. Despite the lack of a significant cytotoxic effect of high glucose under our experimental conditions, our data indicated for the first time that impaired autophagy degradation and inefficient BNIP3-mediated mitophagy may constitute mechanisms underlying neuronal cell damage during chronic hypoxia.

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Section: Discussionmentioning

confidence: 99%

Involvement of impaired autophagy and mitophagy in Neuro-2a cell damage under hypoxic and/or high-glucose conditions

Song

Zou

et al. 2018

Sci Rep

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“…Autophagic structures and/or markers are consistently observed in brain tissue derived from rodent models of acute hypoxic/ischemic brain injury [40,41]. However, controversy exists as to whether autophagy plays a protective or toxic role since both the positive [42,43] and the negative [41,43] modulation of autophagy has been reported to promote neuroprotection using in vivo models of brain ischemia. For instance, genetic silencing of Tuberous Sclerosis Complex 1 (TSC-1), which results in MTORC1 activation and the inhibition of autophagy, exacerbates neuronal injury using in vitro and in vivo models of transient global ischemia [44].…”

Section: Autophagy In the Central Nervous System (Cns)mentioning

confidence: 99%

Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

Plaza-Zabala

Sierra-Torre

Sierra

2017

IJMS

272

210

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Abstract:Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases. Herein, we first describe the basic concepts of autophagy and its regulation, discuss key aspects for its accurate monitoring at the experimental level, and summarize the evidence linking autophagy impairment to CNS senescence and disease. We focus on acute, chronic, and autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer's, Parkinson's, and Huntington's diseases, and multiple sclerosis. Next, we describe the actual and potential impact of autophagy on microglial phagocytic and inflammatory function. Thus, we provide evidence of how autophagy may affect microglial phagocytosis of apoptotic cells, amyloid-β, synaptic material, and myelin debris, and regulate the progression of age-associated neurodegenerative diseases. We also discuss data linking autophagy to the regulation of the microglial inflammatory phenotype, which is known to contribute to age-related brain dysfunction. Overall, we update the current knowledge of autophagy and microglia, and highlight as yet unexplored mechanisms whereby autophagy in microglia may contribute to CNS disease and senescence.

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“…Animals were fed commercially available rodent normal diet or IF (24 h fasting and 24 h feeding) was applied for 2 months according to method by published methods ( 9 , 12 , 17 ). During procedures, food intake of IF group was controlled daily (10 g per day), and body weight of normal diet and IF groups was monitored every week.…”

Section: Methodsmentioning

confidence: 99%

“…Zhu et al ( 11 ), have reporetd that IF protects hippocampal neurons against kainate excitotoxicity in a mouse model of Alzheimer's disease (presenilin1 mutant knockin mice) by reducing oxidative stress. In ischemia, it has been demonstrated that dietary restriction or an IF regimen reduces infarct volume in rodent models of cerebral focal cerebral ischemia by inhibiting the accumulation of autophagosomes in neurons ( 12 ), by suppressing inflammasome activity ( 13 ), and by increasing a preconditioning stress response ( 14 ). The above-mentioned studies attenuate or protect ischemic damage in focal cerebral ischemia models; however, the possibility that IF protects neurons from transient global cerebral ischemia (tGCI) has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Intermittent fasting increases SOD2 and catalase immunoreactivities in the hippocampus but does not protect from neuronal death following transient ischemia in gerbils

Ahn

Noh²,

Shin³

et al. 2018

Mol Med Report

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Intermittent fasting has been shown to have neuroprotective effects against transient focal cerebral ischemic insults. However, the effects of intermittent fasting on transient global ischemic insult has not been studied much yet. The present study examined effects of intermittent fasting on endogenous antioxidant enzyme expression levels in the hippocampus and investigated whether the fasting protects neurons 5 days after 5 min of transient global cerebral ischemia. Gerbils were randomly subjected to either ad libitum or alternate-day intermittent fasting for two months and assigned to sham surgery or transient ischemia. Changes of antioxidant enzymes were examined using immunohistochemistry for cytoplasmic superoxide dismutase 1 (SOD1), mitochondrial (SOD2), catalase (CAT), and glutathione peroxidase (GPX). The effects of intermittent fasting on ischemia-induced antioxidant changes, neuronal damage/degeneration and glial activation were examined. The weight of fasting gerbils was not different from that of control gerbils. In controls, SOD1 and GPX immunoreactivities were strong in pyramidal neurons of filed cornu ammonis 1 (CA1). Transient ischemia in controls significantly decreased expressions of SOD1 and GPX in CA1 pyramidal neurons. Intermittent fasting resulted in increased expressions of SOD2 and CAT, not of SOD1 and GPX, in CA1 pyramidal neurons. Nevertheless, CA1 pyramidal neurons were not protected in gerbils subjected to fasting after transient ischemia, and inhibition of glial-cell activation was not observed in the gerbils. In summary, intermittent fasting for two months increased SOD2 and CAT immunoreactivities in hippocampal CA1 pyramidal neurons. However, fasting did not protect the CA1 pyramidal neurons from transient cerebral ischemia. The results of the present study indicate that intermittent fasting may increase certain antioxidants, but not protect neurons from transient global ischemic insult.

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Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis

Cited by 37 publications

References 34 publications

Involvement of impaired autophagy and mitophagy in Neuro-2a cell damage under hypoxic and/or high-glucose conditions

Involvement of impaired autophagy and mitophagy in Neuro-2a cell damage under hypoxic and/or high-glucose conditions

Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging

Intermittent fasting increases SOD2 and catalase immunoreactivities in the hippocampus but does not protect from neuronal death following transient ischemia in gerbils

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