Intracerebroventricular streptozotocin injection in rats generates acute and chronic effects upon memory and neurodegenerative markers

Author(s)

Taisa de Oliveira Santos

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Psicologia (IP/SBD)
• Defense date: 2010-05-07

Examining board members

Andréa da Silva Torrão; Luiz Roberto Giorgetti de Britto; Carolina Demarchi Munhoz de Souza

• Advisor: Andréa da Silva Torrão

Abstract

Alzheimer´s disease (AD) is the most common cause of dementia in aged humans. Recent reports have suggested a relationship between the onset of AD and an insulin-resistant brain condition. In this context, this study aimed at evaluating the effects of intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats on behavior and neurodegeneration. Four month-old adult male Wistar rats were subjected to bilateral ICV injections of either STZ or vehicle and were tested for both reference and working memories in Morris water maze. After different survival times, rats were subjected to immunoblotting (to evaluate neurodegeneration markers) or to Fluoro-Jade C histochemistry. A marked disruption of performance in working memory was already observed after 3 hours of STZ injections. Immunoblotting analysis showed a significant increase of beta amyloid peptide expression in the amygdala, entorrinal cortex, basal ganglia, and hypothalamus. A significant increase of tau phosphorylation was also observed in the amygdala, cerebellum, cortex, basal forebrain and basal ganglia. Degenerating fibers were seen in the hypothalamus and septal area 1 day postinjection and in CA1 pyramidal neurons and close to the hippocampal dentate gyrus after 15 days. ICV injection of STZ seems therefore to produce an animal model of AD, as it reproduces the characteristic cognitive and histological changes of the disease (AU)

• FAPESP's process: 07/57114-7 - Possible neuroprotective role of the cannabinoid system in a streptozotocin-induced Alzheimer's Disease model
• Grantee: Taisa de Oliveira Santos
• Support Opportunities: Scholarships in Brazil - Master