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

Jeong,Ji  Heun; 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

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

Authors:
- Ji Heun Jeong
- Kwang Sik Yu
- Dong Ho Bak
- Je Hun Lee
- Nam Seob Lee
- Young Gil Jeong
- Dong Kwan Kim
- Jwa‑Jin Kim
- Seung‑Yun Han
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Affiliations: Department of Anatomy, College of Medicine, Konyang University, Seo‑gu, Daejeon 302‑718, Republic of Korea, Department of Physiology, College of Medicine, Konyang University, Seo‑gu, Daejeon 302‑718, Republic of Korea, Department of Anatomy, Brain Research Institute, College of Medicine, Chungnam National University, Jung‑gu, Daejeon 301-747, Republic of Korea
Published online on: October 31, 2016 https://doi.org/10.3892/etm.2016.3852
Pages: 3021-3028

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Abstract

Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF‑treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF‑induced increase was detected in microtubule‑associated protein 1 light chain 3 (LC3)‑II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R‑induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis.

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