Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke
Journal Volume
27
Journal Issue
9
Pages
1497-1513
Date Issued
2018
Author(s)
Kim J.
Kang S.-W.
Mallilankaraman K.
Baik S.-H.
Lim J.C.
Balaganapathy P.
She D.T.
Lok K.-Z.
Fann D.Y.
Thambiayah U.
Stranahan A.M.
Dheen S.T.
Gelderblom M.
Seet R.C.
Karamyan V.T.
Vemuganti R.
Sobey C.G.
Mattson M.P.
Jo D.-G.
Arumugam T.V.
Abstract
Genetic changes due to dietary intervention in the form of either calorie restriction (CR) or intermittent fasting (IF) are not reported in detail until now. However, it is well established that both CR and IF extend the lifespan and protect against neurodegenerative diseases and stroke. The current research aims were first to describe the transcriptomic changes in brains of IF mice and, second, to determine whether IF induces extensive transcriptomic changes following ischemic stroke to protect the brain from injury. Mice were randomly assigned to ad libitum feeding (AL), 12 (IF12) or 16 (IF16) h daily fasting. Each diet group was then subjected to sham surgery or middle cerebral artery occlusion and consecutive reperfusion. Midcoronal sections of ipsilateral cerebral tissue were harvested at the end of the 1 h ischemic period or at 3, 12, 24 or 72 h of reperfusion, and genome-wide mRNA expression was quantified by RNA sequencing. The cerebral transcriptome of mice in AL group exhibited robust, sustained up-regulation of detrimental genetic pathways under ischemic stroke, but activation of these pathways was suppressed in IF16 group. Interestingly, the cerebral transcriptome of AL mice was largely unchanged during the 1 h of ischemia, whereas mice in IF16 group exhibited extensive up-regulation of genetic pathways involved in neuroplasticity and down-regulation of protein synthesis. Our data provide a genetic molecular framework for understanding how IF protects brain cells against damage caused by ischemic stroke, and reveal cellular signaling and bioenergetic pathways to target in the development of clinical interventions. ? The Author(s) 2018. Published by Oxford University Press. All rights reserved.
SDGs
Other Subjects
messenger RNA; transcriptome; transcriptome; animal experiment; animal model; animal tissue; Article; brain cell; brain injury; brain ischemia; brain perfusion; brain tissue; controlled study; diet restriction; down regulation; human; male; middle cerebral artery occlusion; mouse; nerve cell plasticity; nonhuman; priority journal; protein synthesis; RNA sequence; sham procedure; signal transduction; transcriptomics; upregulation; animal; brain ischemia; C57BL mouse; caloric restriction; diet restriction; genetics; physiology; sequence analysis; Animals; Brain Ischemia; Caloric Restriction; Fasting; Male; Mice; Mice, Inbred C57BL; Sequence Analysis, RNA; Signal Transduction; Transcriptome
Type
journal article