Studies for Improving a Rat Model of Alzheimer’s Disease: Icv Administration of Well-Characterized β-Amyloid 1-42 Oligomers Induce Dysfunction in Spatial Memory

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 11; p. 2007
• Main Authors: Kasza, Ágnes, Penke, Botond, Frank, Zsuzsanna, Bozsó, Zsolt, Szegedi, Viktor, Hunya, Ákos, Németh, Klaudia, Kozma, Gábor, Fülöp, Lívia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.11.2017; MDPI
• Subjects: AD rat model; Alzheimer Disease - drug therapy; Alzheimer Disease - physiopathology; amyloid beta; Amyloid beta-Peptides - administration & dosage; Amyloid beta-Peptides - therapeutic use; Animal memory; Animals; Disease Models, Animal; Golgi staining; hippocampus; icv administration; long-term potentiation; Male; Maze Learning - drug effects; Morris water maze; Rats; Rodents; spatial memory; Spatial Memory - drug effects; Morris water maze; AD rat model; hippocampus; Golgi staining; spatial memory; icv administration; amyloid beta; long-term potentiation
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22112007

During the past 15 years, several genetically altered mouse models of human Alzheimer’s disease (AD) have been developed. These costly models have greatly facilitated the evaluation of novel therapeutic approaches. Injecting synthetic β-amyloid (Aβ) 1-42 species into different parts of the brain of non-transgenic rodents frequently provided unreliable results, owing to a lack of a genuine characterization of the administered Aβ aggregates. Previously, we have published a new rat AD-model in which protofibrillar-fibrillar Aβ1-42 was administered into rat entorhinal cortex (Sipos 2007). In order to develop a more reliable model, we have injected well-characterized toxic soluble Aβ1-42 species (oligomers, protofibrils and fibrils) intracerebroventricularly (icv) into rat brain. Studies of the distribution of fluorescent-labeled Aβ1-42 in the brain showed that soluble Aβ-species diffused into all parts of the rat brain. After seven days, the Aβ-treated animals showed a significant decrease of spatial memory in Morris water maze test and impairment of synaptic plasticity (LTP) measured in acute hippocampal slices. The results of histological studies (decreased number of viable neurons, increased tau levels and decreased number of dendritic spines) also supported that icv administration of well-characterized toxic soluble Aβ species into rat brain provides a reliable rat AD-model.