Human Molecular Genetics
Human Molecular Genetics
5 years ago

Transcriptome Analysis Reveals Intermittent Fasting-Induced Genetic Changes in Ischemic Stroke.

Sung-Chun Tang, Vardan T Karamyan, Sung-Wook Kang, Dong-Gyu Jo, S Thameem Dheen, Mark P Mattson, Sang-Ha Baik, Thiruma V Arumugam, Uma Thambiayah, Ker-Zhing Lok, James C Lim, Christopher G Sobey, Raymond C Seet, Joonki Kim, Karthik Mallilankaraman, Alexis M Stranahan, Mathias Gelderblom, David Y Fann, Priyanka Balaganapathy, Raghu Vemuganti, David T She
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) hours daily fasting. Each diet group was then subjected to sham surgery or middle cerebral artery occlusion and consecutive reperfusion. Mid-coronal sections of ipsilateral cerebral tissue were harvested at the end of the 1 hour ischemic period or at 3, 12, 24 or 72 hours 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 hour 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.

Publisher URL: http://doi.org/10.1093/hmg/ddy057

DOI: 10.1093/hmg/ddy057

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