title: Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice.
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.
authors.affiliation: Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314-6399, USA.
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhihou
authors.initials: Z
authors.lastname: Liang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Tian
authors.forename: Julie
authors.initials: J
authors.lastname: Blanchard
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Dai
authors.forename: Sonia
authors.initials: S
authors.lastname: Chalbot
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Cheng-Xin
authors.initials: CX
authors.lastname: Gong
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007276:Injections, Intraventricular; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D013311:Streptozocin