Abstract

Background:
Alzheimer's disease (AD) is a neurodegenerative condition, and the number of cases is projected to rise each year. Developing an Alzheimer's disease animal model has a major impact in studying the pathology of the disease and in developing therapies and treatments

Aim:
This study aimed to create an Alzheimer's disease animal model using the C3H mice by administering trimethyltin (TMT) via intraperitoneal injection (IP). The findings were supported by hematological analysis, pathology, protein biomarkers, and behavioral assessments.

Methods:
In this experiment, there are two groups: a non-treated group (normal mouse) and a treatment group (AD animal model). Each group consists of four male C3H mice, aged eight weeks. The treatment group was injected intraperitoneally with 2.5 mg/kg of body weight TMT. Hematological analyses were conducted to assess the blood routine, while pathological changes in brain structure, particularly in the hippocampus, were examined using Hematoxylin and Eosin staining as well as Nissl staining. Additionally, protein biomarkers associated with Alzheimer's disease were analyzed through proteomic profiling via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Behavioral analysis was conducted using the radial arm maze.

Results:
Hematological analysis revealed an increase in hematocrit, mean corpuscular volume, leucocytes, and neutrophil levels, while other parameters remained within the normal range. Histopathological analysis revealed neuronal loss and structural alterations in the pyramidal cell layers of the cornu ammonis 1 (CA1) and cornu ammonis 3 (CA3), presence of inflammation, and neurofibrillary tangles. Proteomic analysis identified several protein biomarkers related with Alzheimer’s disease in the AD animal model, including amyloid beta, tau protein, apolipoprotein E (ApoE), and TREM3. Behavioral analysis demonstrated significant cognitive and memory declines in AD animal models compared to non-treated animals.

Conclusion:
The intraperitoneal administration of Trimethyltin in C3H mice effectively induces pathological changes in the brain that are related to Alzheimer’s disease. The observed pathological and behavioral changes in this AD animal model resemble those found in human cases of the disease. This model can serve as a valuable platform for studying the etiology, pathogenesis, and pathophysiology of Alzheimer's disease, as well as testing new therapies.

Key words: Alzheimer’s disease; Animal model; C3H mice; Trimethyltin.