2-deoxyglucose induces beta-APP overexpression, tau hyperphosphorylation and expansion of the trans-part of the Golgi complex in rat cerebral cortex.
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.
Grieb
Pawel
P
Laboratory of Experimental Pharmacology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. pgrieb@cmdik.pan.pl.
Gordon-Krajcer
Wanda
W
Frontczak-Baniewicz
Małgorzata
M
Walski
Michał
M
Ryba
Miroslaw S
MS
Kryczka
Tomasz
T
Fiedorowicz
Michal
M
Kulinowski
Piotr
P
Sułek
Zenon
Z
Majcher
Katarzyna
K
Jasiński
Andrzej
A
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*
D016564:Amyloid beta-Protein Precursor; D000963:Antimetabolites; D016875:tau Proteins; D003847:Deoxyglucose