Intracerebroventricular Streptozotocin Exacerbates Alzheimer-like Changes of 3xTg-AD Mice

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2013 Sep 3

PMID 23996345

Citations 44

Authors

Yanxing Chen

Zhihou Liang

Zhu Tian

Julie Blanchard

Chun-Ling Dai

Sonia Chalbot

Khalid Iqbal

Fei Liu

Cheng-Xin Gong

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) involves several possible molecular mechanisms, including impaired brain insulin signaling and glucose metabolism. To investigate the role of metabolic insults in AD, we injected streptozotocin (STZ), a diabetogenic compound if used in the periphery, into the lateral ventricle of the 6-month-old 3xTg-AD mice and studied the cognitive function as well as AD-like brain abnormalities, such as tau phosphorylation and Aβ accumulation, 3-6 weeks later. We found that STZ exacerbated impairment of short-term and spatial reference memory in 3xTg-AD mice. We also observed an increase in tau hyperphosphorylation and neuroinflammation, a disturbance of brain insulin signaling, and a decrease in synaptic plasticity and amyloid β peptides in the brain after STZ treatment. The expression of 20 AD-related genes, including those involved in the processing of amyloid precursor protein, cytoskeleton, glucose metabolism, insulin signaling, synaptic function, protein kinases, and apoptosis, was altered, suggesting that STZ disturbs multiple metabolic and cell signaling pathways in the brain. These findings provide experimental evidence of the role of metabolic insult in AD.

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