Desensitization of brain insulin receptor. Effect on glucose/energy and related metabolism.
The overall majority of cases of Alzheimer disease are not caused by genetic abnormalities. A pluricausal etiology is assumed, and the age factor may be of pivotal significance. Aging leads to inherent changes in basic metabolic principles, including the functionally most important cerebral glucose/energy metabolism. Experimentally induced perturbation of the neuronal control over the glucose metabolism by means of intracerebroventricular administration of streptozotocin leads to cascade-like abnormalities in glucose breakdown and energy formation and in membrane phospholipid and monoaminergic catecholamine metabolism, which closely resemble the disturbances found in sporadic Alzheimer disease. It is concluded that this model is a good tool for in vivo study of the cellular events characteristic for this human neurodegenerative disorder.
Hoyer
S
S
Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Federal Republic of Germany.
Müller
D
D
Plaschke
K
K
D000375:Aging; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology*; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity*
D015306:Biogenic Monoamines; D008563:Membrane Lipids; D010743:Phospholipids; D013311:Streptozocin; D006003:Glycogen; D011972:Receptor, Insulin; D005947:Glucose