Early and late neurodegeneration and memory disruption after intracerebroventricular streptozotocin

• Published in: Physiology & behavior 2012-10, Vol.107 (3), p.401-413
• Main Authors: Santos, Taisa de Oliveira, Mazucanti, Caio Henrique Yokoyama, Xavier, Gilberto Fernando, Torrão, Andréa da Silva
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Aging; Alzheimer disease; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Analysis of Variance; animal models; Animals; Behavioral psychophysiology; Biological and medical sciences; Blood Glucose; Choline O-Acetyltransferase - metabolism; Cognitive dysfunction; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; etiology; Fluoresceins; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Glial Fibrillary Acidic Protein - metabolism; glucose; Glucose/energy metabolism; hippocampus; histochemistry; immunoblotting; Injections, Intraventricular; insulin; Learning/memory; Male; Maze Learning - drug effects; Medical sciences; memory; Memory Disorders - chemically induced; Memory, Short-Term - drug effects; metabolism; Motor Activity - drug effects; Neurodegeneration; Neurodegenerative Diseases - chemically induced; Neurology; Organic mental disorders. Neuropsychology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Wistar; Reaction Time - drug effects; Streptozocin - administration & dosage; Streptozotocin; tau Proteins - metabolism; Time Factors
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2012.06.019

Abstract 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.