A Neonatal Mild Defect in Brain Insulin Signaling Predisposes a Subclinical Model of Sporadic Alzheimer's to Develop the Disease

Authors
Z Abbasi, MMG Seno, M FereidoniÊ

Lab
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

Journal
Journal of Molecular Neuroscience

Abstract
Brain insulin system dysfunction has been proposed as a key player in the pathogenesis of sporadic AlzheimerÕs disease (sAD). Given this fact, an adult rat model for sAD has been developed by intracerebroventricular injection of a subdiabetogenic streptozotocin dosage (icv-STZ). A low dose of icv-STZ in adult rats leads to a subclinical model of AlzheimerÕs disease. According to the brain developmental origin for sAD occurrence, the present study evaluated the effect of neonatal injection of icv-STZ on the development and progression of AlzheimerÕs disease later in the adult animals treated with a low dose of icv-STZ. Although no alteration was observed in the rats receiving an adult low dose of icv-STZ, these animals displayed cognitive deficits if they were also treated neonatally with icv-STZ. These impairments were associated with altered gene expression of insulin receptor, tau and choline acetyltransferase, along with increased astrocyte and dark neuron densities in the hippocampus. This study highlights neonatal brain insulin system dysfunction in the programming of brain insulin signaling sensitivity and provides more evidence for the developmental origin of sAD.

BIOSEB Instruments Used:
Rotarod (BX-ROD),Aron Test or Four Plates Test (LE830)