PMID- 25678460 OWN - NLM STAT- MEDLINE DCOM- 20160307 LR - 20181113 IS - 1543-706X (Electronic) IS - 1071-2690 (Linking) VI - 51 IP - 6 DP - 2015 Jun TI - Caloric restriction mimetic 2-deoxyglucose maintains cytoarchitecture and reduces tau phosphorylation in primary culture of mouse hippocampal pyramidal neurons. PG - 546-55 LID - 10.1007/s11626-015-9867-1 [doi] AB - Typical form of neurons is crucially important for their functions. This is maintained by microtubules and associated proteins like tau. Hyperphosphorylation of tau is a major concern in neurodegenerative diseases. Glycogen synthase kinase3beta (GSK3beta) and cyclin-dependent protein kinase 5 (Cdk5) are the enzymes that govern tau phosphorylation. Currently, efforts are being made to target GSK3beta and Cdk5 as possible therapeutic avenues to control tau phosphorylation and treat neurodegenerative diseases related to taupathies. In a number of studies, caloric restriction mimetic 2-deoxyglucose (C6H12O5) was found to be beneficial in improving the brain functions. However, no reports are available on the effect of 2-deoxyglucose 2-DG on tau phosphorylation. In the present study, hippocampal pyramidal neurons from E17 mouse embryos were isolated and cultured on poly-L-lysine-coated coverslips. Neurons from the experimental group were treated with 10 mM 2-deoxyglucose. The treatment of 2-DG resulted in healthier neuronal morphology in terms of significantly lower number of cytoplasmic vacuoles, little or no membrane blebbings, maintained axon hillock and intact neurites. There were decreased immunofluorescence signals for GSK3beta, pTau at Ser262, Cdk5 and pTau at Ser235 suggesting decreased tau phosphorylation, which was further confirmed by Western blotting. The results indicate the beneficial effects of 2-DG in controlling the tau phosphorylation and maintaining the healthy neuronal cytoarchitecture. FAU - Bele, M S AU - Bele MS AD - Cellular stress response laboratory, Cell Biology Division, Department of Zoology, Shivaji University, Kolhapur, India. FAU - Gajare, K A AU - Gajare KA FAU - Deshmukh, A A AU - Deshmukh AA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150213 PL - Germany TA - In Vitro Cell Dev Biol Anim JT - In vitro cellular & developmental biology. Animal JID - 9418515 RN - 0 (Microtubule-Associated Proteins) RN - 0 (Mtap2 protein, mouse) RN - 0 (tau Proteins) RN - 9G2MP84A8W (Deoxyglucose) RN - EC 2.7.11.1 (Cyclin-Dependent Kinase 5) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Gsk3b protein, mouse) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) SB - IM MH - Animals MH - Blotting, Western MH - *Caloric Restriction MH - Cells, Cultured MH - Cyclin-Dependent Kinase 5/metabolism MH - Deoxyglucose/*pharmacology MH - Fluorescent Antibody Technique MH - Glycogen Synthase Kinase 3/metabolism MH - Glycogen Synthase Kinase 3 beta MH - Hippocampus/*cytology MH - Mice MH - Microtubule-Associated Proteins/metabolism MH - Phosphorylation/drug effects MH - Pyramidal Cells/*cytology/drug effects/*metabolism MH - tau Proteins/*metabolism EDAT- 2015/02/14 06:00 MHDA- 2016/03/08 06:00 CRDT- 2015/02/14 06:00 PHST- 2014/08/25 00:00 [received] PHST- 2015/01/01 00:00 [accepted] PHST- 2015/02/14 06:00 [entrez] PHST- 2015/02/14 06:00 [pubmed] PHST- 2016/03/08 06:00 [medline] AID - 10.1007/s11626-015-9867-1 [doi] PST - ppublish SO - In Vitro Cell Dev Biol Anim. 2015 Jun;51(6):546-55. doi: 10.1007/s11626-015-9867-1. Epub 2015 Feb 13.