Streptozotocin (STZ) through the intraperitoneal route is used as a diabetic
model, while intracerebroventricular (ICV) STZ administration in rodents is a model
for sporadic Alzheimer's disease (AD). It majorly induces insulin resistance along with
oxidative stress, mitochondrial dysfunction, and neuroinflammation in prime brain
regions of the cortex and hippocampus. The significant pathological hallmarks in AD
are phosphorylated tau protein generated neurofibrillary tangles and amyloid plaques
which are also observed in this model. The ICV-STZ model can be validated through
various behavioral, biochemical, mitochondrial, molecular, and histopathological
analyses. The potential target molecules in the insulin signaling pathway could include
IR, IRS-1, PI3K, AKT, GSK-3β, etc. In a nutshell, we can say that the ICV-STZ model
is quite robust for insulin-resistant sporadic AD; however, there are a few limitations
like mortality and the requirement of sophisticated procedure.
Keywords: Alzheimer`s disease, Amyloid plaques, ICV-STZ, Insulin resistance,
Oxidative stress, Tau protein.
