title: Long-term abnormalities in brain glucose/energy metabolism after inhibition of the neuronal insulin receptor: implication of tau-protein.
abstract: The triplicate intracerebroventricular (icv) application of the diabetogenic compound streptozotocin (STZ) in low dosage was used in 1-year-old male Wistar rats to induce a damage of the neuronal insulin signal transduction (IST) system and to investigate the activities of hexokinase (HK), phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GDH), pyruvate kinase (PK), lactate dehydrogenase (LDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) in frontoparietotemporal brain cortex (ct) and hippocampus (h) 9 weeks after damage. In parallel, the concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), guanosine triphosphate (GTP) and creatine phosphate (CrP) were determined. We found reductions of HK to 53% (ct) and 60% (h) of control, PFK to 63/64% (ct/h); GDH to 56/61% (ct/h), PFK to 57/59% (ct/h), alpha-KGDH to 37/35% (ct/h) and an increase of LDH to 300/240% (ct/h). ATP decreased to 82/87% (ct/h) of control, GTP to 69/81% (ct/h), CrP to 82/81% (ct/h), approximately P to 82/82% (ct/h), whereas ADP increased to 189/154% (ct/h). The fall of the activities of the glycolytic enzymes HK, PFK, GDH and PK was found to be more marked after 9 weeks of damage when compared with 3- and 6-week damage whereas the diminution in the concentration of energy rich compound was stably reduced by between 20 and 10% relative to control. The abnormalities in glucose/energy metabolism were discussed in relation to tau-protein mismetabolism of experimental animals, and of sporadic AD.
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany. siegfried_hoyer@med.uni-heidelberg.de
authors.forename: S
authors.initials: S
authors.lastname: Hoyer
authors.forename: H
authors.initials: H
authors.lastname: Lannert
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D004734:Energy Metabolism / Q000187:drug effects*; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D025221:Phosphofructokinases / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D010725:Phosphocreatine; D013311:Streptozocin; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); D007655:Ketoglutarate Dehydrogenase Complex; D025221:Phosphofructokinases; D006593:Hexokinase; D011770:Pyruvate Kinase; D011972:Receptor, Insulin