The Intermittent Fasting Mimetic, 2-deoxyglucose, Reprograms Brain Derived Neurotrophic Factor (BDNF) transcription via an Adaptive ER Stress-ATF4 Pathway and Improves Outcomes in Alzheimer's and Stroke Models [RNA-seq]

In our preliminary in-vitro studies in primary neurons, we found that changing glucose utlization using 2-deoxyglucose (2-DG, a known glycolytic inhibitor, which inhibits glucose utilization) led to a dose dependent signficant increase in Bdnf gene expression. Additionally, the dose of 2-DG that induced Bdnf gene expression also normalized learning and memory in mouse model of AD (5xFAD mouse) and improved functional recovery in mice models of ischemic and hemorrhagic strokes. With RNA Sequencing of 2-DG treated primary neuronal samples, our first goal was to identify dominant gene signatures in response to 2-deoxyglucose in order to delineate critical pathways affected by changes in glucose metabolism and our second goal was to understand if 2-deoxyglucose affect a broad gene plasticity program or only a few selective plasticity genes. Overall design: Primary immature neurons were treated with either 1mM 2-DG or 10mM 2-DG for 6h and a parallel untreated set of primary immature neurons were used as a control. Thereafter, RNA was extracted using Nucleospin RNA kit (Macherey-Nagel) and follwing its protocol. Three independent replicates were used for the study.