Injection of insulin amyloid fibrils in the hippocampus of male Wistar rats: report on memory impairment and formation of amyloid plaques

Abstract

Amyloid fibrils result from a particular type of protein aggregation, and have been linked with various disorders, including neurodegenerative ones. In the case of Alzheimer's disease, amyloid beta (abeta) fibrils are detected in patients' brain, in the amyloid plaques. These fibrils can be produced in vitro, and their injection into animals' brains generates an animal model of Alzheimer's disease. Based on the structural similarity of amyloid fibrils that are formed from different proteins, we hypothesized that injecting insulin amyloid fibrils into rats' brains could result in amyloid plaque formation. Fourteen male Wistar rats were divided into control and experimental groups (n = 7). The experimental group was bilaterally injected with insulin amyloid in the hippocampus. Seven days after injection, a shuttle box test was performed and the experimental group's memory was found to be impaired. Histological investigation of these rats' brain showed the formation of amyloid plaques in the hippocampus. A limited test has provided preliminary evidence for the stability of these plaques up to 35 days. Further complementary studies are required to fully validate the proposed procedure, which is simple and relatively low cost, and could be suggested as an alternative to models generated with abeta fibrils.

Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids

“…In addition to behaving similar to Aβ, model proteins have other advantages such as high stability and high reproducibility ( 20 ). From our previous study, we knew that bilateral injection of insulin amyloid fibrils into the hippocampus can generate formation of AD plaques in male rats, which also show reduced memory ( 13 ). Our present results in the model group are in good agreement with these studies, both behaviorally and histologically.…”

“…A mixture of insulin fibril and trans- chalcone was injected according to Table 1 with a Hamilton syringe. The injection rate was 0.5 μg/min ( 13 ). At the end of the third week after surgery, all groups underwent behavioral tests related to learning and memory.…”

Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability

“…Therefore, Aβ1–42 was adopted for the present experiments. Formerly, intra-cerebroventricular injection was widely used to investigated the toxicity of Aβ1–42 in numerous studies (28,29); however, this delivery method has numerous disadvantages, including drug diffusion, inaccurate positioning and relatively high cost (10,30). Intra-hippocampal administration effectively avoided these shortcomings and shortened delivery time significantly in the present study.…”

Modeling and simulation in medical sciences: an overview of specific applications based on research experience in EMRI (Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences)

“…Candidate ligands that were administered to the AD animal models, and could attenuate their symptoms to some extent included indole and trans-chalcone [96], sylimarin [97], metformin [98], thymol [99], and eugenol [100]. Based on our experience in generating amyloid structures in insulin, we have also proposed a modification in the generation of rodent AD-like model : instead of injecting abeta amyloids to the animals brains, we used insulin amyloids which are easier formed at a lower cost [101].…”