RGD Reference Report - Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease.

Authors: Lester-Coll, N  Rivera, EJ  Soscia, SJ  Doiron, K  Wands, JR  De la Monte, SM 
Citation: Lester-Coll N, etal., J Alzheimers Dis. 2006 Mar;9(1):13-33.
RGD ID: 5509963
Pubmed: PMID:16627931   (View Abstract at PubMed)

The cascade of Alzheimer's disease (AD) neurodegeneration is associated with persistent oxidative stress, mitochondrial dysfunction, impaired energy metabolism, and activation of pro-death signaling pathways. More recently, studies with human postmortem brain tissue linked many of the characteristic molecular and pathological features of AD to reduced expression of the insulin and insulin-like growth factor (IGF) genes and their corresponding receptors. We now demonstrate using an in vivo model of intracerebral Streptozotocin (ic-STZ), that chemical depletion of insulin and IGF signaling mechanisms combined with oxidative injury is sufficient to cause AD-type neurodegeneration. The ic-STZ-injected rats did not have elevated blood glucose levels, and pancreatic architecture and insulin immunoreactivity were similar to control, yet their brains were reduced in size and exhibited neurodegeneration associated with cell loss, gliosis, and increased immunoreactivity for p53, active glycogen synthase kinase 3beta, phospho-tau, ubiquitin, and amyloid-beta. Real time quantitative RT-PCR studies demonstrated that the ic-STZ-treated brains had significantly reduced expression of genes corresponding to neurons, oligodendroglia, and choline acetyltransferase, and increased expression of genes encoding glial fibrillary acidic protein, microglia-specific proteins, acetylcholinesterase, tau, and amyloid precursor protein. These abnormalities were associated reduced expression of genes encoding insulin, IGF-II, insulin receptor, IGF-I receptor, and insulin receptor substrate-1, and reduced ligand binding to the insulin and IGF-II receptors. These results demonstrate that many of the characteristic features of AD-type neurodegeneration can be produced experimentally by selectively impairing insulin/IGF functions together with increasing oxidative stress, and support our hypothesis that AD represents a neuro-endocrine disorder associated with brain-specific perturbations in insulin and IGF signaling mechanisms, i.e. Type 3 diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease  ISOIgf2 (Rattus norvegicus)5509963; 5509963mRNA:decreased expression:brainRGD 
Alzheimer's disease  ISOInsr (Rattus norvegicus)5509963; 5509963mRNA:decreased expression:brainRGD 
Alzheimer's disease  IEP 5509963; 5509963mRNA:decreased expression:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf2  (insulin-like growth factor 2)
Insr  (insulin receptor)

Genes (Mus musculus)
Igf2  (insulin-like growth factor 2)
Insr  (insulin receptor)

Genes (Homo sapiens)
IGF2  (insulin like growth factor 2)
INSR  (insulin receptor)


Additional Information