Insulin-resistant brain state: the culprit in sporadic Alzheimer's disease?
Severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease (sAD) pathology. Indeed, the "insulin-resistant brain state" has been hypothesized to form the core of the neurodegenerative events that occur in sAD. In this vein, intracerebroventricular administration of subdiabetogenic doses of streptozotocin (STZ) in rats can induce an insulin-resistant brain state, which is proposed as a suitable experimental model of sAD. This review highlights the involvement of disturbed brain insulin metabolism in sAD etiopathogenesis. Furthermore, current knowledge demonstrates that central STZ administration produces brain pathology and behavioral changes that resemble changes found in sAD patients. The STZ-intracerebroventricularly treated rat represents a promising experimental tool in this field by providing new insights concerning early brain alterations in sAD, which can be translated in novel etiopathogenic and therapeutic approaches in this disease.
Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, Portugal.
Sónia C
SC
Correia
Renato X
RX
Santos
George
G
Perry
Xiongwei
X
Zhu
Paula I
PI
Moreira
Mark A
MA
Smith
D000544:Alzheimer Disease / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D007276:Injections, Intraventricular; D007328:Insulin / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000008:administration & dosage* / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin
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