Animal Models for Neurological Disorders

Intracerebroventricular-Streptozotocin Induced Insulin Resistant In Vivo Model of Sporadic Alzheimer's Disease: Pathophysiological Aspects and Potential Therapeutic Targets

Author(s): Ansab Akhtar and Sangeeta Pilkhwal Sah *

Pp: 208-226 (19)

DOI: 10.2174/9789815039689121010013

* (Excluding Mailing and Handling)


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.

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