Molecular and cellular mechanisms of sporadic Alzheimer’s disease: Studies on rodent models in vivo

Abstract

In this review, recent data are presented on molecular and cellular mechanisms of pathogenesis of the most widespread (about 95%) sporadic forms of Alzheimer's disease obtained on in vivo rodent models. Although none of the available models can fully reproduce the human disease, several key molecular mechanisms (such as dysfunction of neurotransmitter systems, especially of the acetylcholinergic system, β-amyloid toxicity, oxidative stress, neuroinflammation, mitochondrial dysfunction, disturbances in neurotrophic systems) are confirmed with different models. Injection models, olfactory bulbectomy, and senescence accelerated OXYS rats are reviewed in detail. These three approaches to in vivo modeling of sporadic Alzheimer's disease have demonstrated a considerable similarity in molecular and cellular mechanisms of pathology development. Studies on these models provide complementary data, and each model possesses its specific advantages. A general analysis of the data reported for the three models provides a multifaceted and the currently most complete molecular picture of sporadic Alzheimer's disease. This is highly relevant also from the practical viewpoint because it creates a basis for elaboration and preclinical studies of means for treatment of this disease.

Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies

“…injections of streptozotocin (STZ) [47,118], subcutaneous (s.c.) injections of D-galactose [78,119], i.p. injections of MK-801 (a non-competitive NMDA receptor antagonist) [120], olfactory bulbectomy (OBE) [121] and i.c.v. injections of lipopolysaccharide (LPS) [116,[122][123][124] or colchicine [116].…”

Epicatechin Reduces Spatial Memory Deficit Caused by Amyloid-β25–35 Toxicity Modifying the Heat Shock Proteins in the CA1 Region in the Hippocampus of Rats

“…Oxidative stress is considered a key factor in the AD pathogenesis [28]. Aβ is responsible for promoting the generation of ROS, the oxidation of lipids to destabilize the neuronal membrane, and decreasing the activity of antioxidant enzymes such as SOD and catalase, which encourage the necrosis and apoptosis states [29]. Reports indicate that Aβ 25–35 interacts with the cell membrane, altering the structure and function of the lipid bilayer and augmenting the concentration of ROS and lipid peroxidation, as shown in our results.…”

“…Therefore, it is suggested that Aβ 25–35 promotes an inflammatory response mediated by the production of proinflammatory cytokines, which could trigger the generation of ROS and the proliferation of glial cells, leading to reactive gliosis [43]. All these mechanisms of neurodegeneration cause damage to the structure and function of the limbic system, particularly in the Hp, a brain region that has a key role in the development of spatial memory, in such a way that a characteristic of the neurotoxicity of Aβ 25–35 is the deterioration in learning and spatial memory, which is supported by a large number of publications [17,18,24,28,29].…”

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

“…Modeling of cholinergic dysfunction allows to reproduce memory impairments, which are among the central symptoms of AD associated dementia. Several neurotoxic substances were used in order to produce loss of BFCN in animals [99]. Till the mid of 1990 s, ethylcholine aziridinium ion (AF64A) was widely used for this purpose, the toxin with a structure similar to that of choline.…”