Early and late neurodegeneration and memory disruption after intracerebroventricular streptozotocin

Glucose metabolism and insulin signaling disruptions in the brain have been proposed as a likely etiology of Alzheimer's disease. The aim of the present study was to investigate the time course of cognitive impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and correlate them with the ensuing neurodegenerative process. Early and late effects of STZ were evaluated by using the reference and working memory versions of the Morris' water maze task and the evaluation of neurodegenerative markers by immunoblotting and the Fluoro-Jade C histochemistry. The results revealed different types of behavioral and neurodegenerative responses, with distinct time courses. We observed an early disruption on the working memory as early as 3 h after STZ injections, which was followed by degenerative processes in the hippocampus at 1 and 15 days after STZ injections. Memory disruption increases over time and culminates with significant changes in amyloid-beta peptide and hyperphosphorylated Tau protein levels in distinct brain structures. These findings add information on the Alzheimer's disease-like STZ animal model and on the mechanisms underlying neurodegenerative processes.

Highlights► Intracerebroventricular streptozotocin impairs the reference and working memories. ► Working memory is disrupted as early as 3 h after STZ injection. ► Neuron degeneration was observed in hippocampus after 1 and 15 days of the injection. ► βA peptide expression increases in the hippocampus, entorhinal cortex, and basal ganglia. ► Hyperphosphorylated Tau was seen in the entorhinal cortex, neocortex, and basal ganglia.