title: 2-deoxyglucose induces beta-APP overexpression, tau hyperphosphorylation and expansion of the trans-part of the Golgi complex in rat cerebral cortex.
abstract: The effects of a single intraperitoneal injection of a non-metabolizable glucose analog 2-deoxyglucose (2-DG, 500 mg/kg) on the levels of beta-APP expression, and phosphorylated and unphosphorylated tau protein in the rat cerebral cortex were investigated. The effects of 2-DG on the ultrastructure of cortical neurons with particular emphasis on the morphology of the Golgi apparatus, and on brain bioenergetics assessed by in vivo 31P-MRS technique were also evaluated. Seven and a half hours after injection of 2-deoxyglucose a significant increase in brain cortex beta-APP expression, increased tau phosphorylation, and a marked relative expansion of the trans- part of the Golgi intracellular secretory pathway in cortical neurons has been found. The changes of beta-APP expression and tau phosphorylation appeared within 1 h after 2-DG application and continued for at least 24 h. However, brain 31P resonance spectra remained unchanged for up to 7.5 h after 2-DG. It is suggested that the increase of beta-APP expression represents a response of brain tissues to 2-DG-evoked biochemical stress, while tau hyperphosphorylation and the change in Golgi morphology may be secondary phenomena.
authors.affiliation: Laboratory of Experimental Pharmacology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. pgrieb@cmdik.pan.pl.
authors.forename: Pawel
authors.initials: P
authors.lastname: Grieb
authors.forename: Wanda
authors.initials: W
authors.lastname: Gordon-Krajcer
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Frontczak-Baniewicz
authors.forename: Michał
authors.initials: M
authors.lastname: Walski
authors.forename: Miroslaw S
authors.initials: MS
authors.lastname: Ryba
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kryczka
authors.forename: Michal
authors.initials: M
authors.lastname: Fiedorowicz
authors.forename: Piotr
authors.initials: P
authors.lastname: Kulinowski
authors.forename: Zenon
authors.initials: Z
authors.lastname: Sułek
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Majcher
authors.forename: Andrzej
authors.initials: A
authors.lastname: Jasiński
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D003847:Deoxyglucose / Q000633:toxicity*; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D000963:Antimetabolites; D016875:tau Proteins; D003847:Deoxyglucose