A Rat Model of Alzheimer’s Disease Based on Abeta42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems

Abstract

Alzheimer’s disease (AD) is one of the most serious human, medical, and socioeconomic burdens. Here we tested the hypothesis that a rat model of AD (Samaritan; Taconic Pharmaceuticals, USA) based on the application of amyloid beta42 (Abeta42) and the pro-oxidative substances ferrous sulfate heptahydrate and L-buthionine-(S, R)-sulfoximine, will exhibit cognitive deficits and disruption of the glutamatergic and cholinergic systems in the brain. Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function. Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately. Our results show that Samaritan rats™ exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory. Moreover, Samaritan rats exhibited significant changes in NR2A expression and CHT1 activity compared to controls rats, mimicking the situation in patients with early stage AD. Taken together, our results corroborate the hypothesis that Samaritan rats are a promising model of AD in its early stages.

Acute and Chronic Sleep Deprivation-Related Changes in N-methyl-D-aspartate Receptor—Nitric Oxide Signalling in the Rat Cerebral Cortex with Reference to Aging and Brain Lateralization

“…After, all blots were washed in PBS buffer/TBS buffer and incubated for 1 h with a horseradish peroxidase-conjugated secondary antibody (Dako, Santa Clara, CA, USA, 1:3000, for α-tubulin—dilution of 1:5000 was used). Detections were performed with a chemiluminescent substrate (ThermoFisher Scientific, Walthman, MA, USA) and evaluated by the Gel Doc Analysis system (Bio-Rad, Hercules, CA, USA), in accordance with our previous studies [29,36].…”

“…With respect to brain lateralization, our earlier analysis did not reveal significant differences between the right (R) and left (L) frontal cortices of young male Sprague-Dawley rats in NR1, NR2A, or NR2B subunit expressions [29]. Only mild L/R laterality (index of laterality < +0.100) was found in NR2B expression in the frontal cortex of young male Long Evans rats [36]. On the other hand, there seems to be the same asymmetry in NR2B expression in the hippocampus, reported at a synaptic level [37].…”

Lipopolysaccharide-Induced Memory Impairment in Rats: a Model of Alzheimer’s Disease

“…There are several other non-genetically manipulated rat models of AD which are not limited to induced neuroinflammation. For example, the ferrous amyloid buthionine (FAB) rat model (Lecanu and Papadopoulos 2013), the sodium azide model (Szabados et al 2004) and the Samaritan AD rat model (Petrasek et al 2016). This review focuses only on the widely studied LPS-induced cognitive deficit in rats and the possible factors that can influence rats' response to LPS.…”

The McGill Transgenic Rat Model of Alzheimer's Disease Displays Cognitive and Motor Impairments, Changes in Anxiety and Social Behavior, and Altered Circadian Activity

“…Cognitive function impairments are the hallmark of human AD. We performed a task focused on delay-dependent forgetting in the Morris water maze, and also the passive and active place avoidance tasks in the carousel maze, a paradigm known to be sensitive to AD-related impairments (Petrasek et al, 2016 ), but never before applied to this particular model. As those tasks tap different aspects of spatial cognition, they provide complementary information, and are well-suited for inclusion in testing batteries, as previous experience with one of them does not affect the performance in the other, as shown by Vojtechova et al ( 2016 ).…”