Dinda Aliffia, Hevi Wihadmadyatami, Muhammad Z. Z. Raihan, Ulayatul Kustiati, Wilda B. T. Sanjaya, Anisa P. Aviana, Dwi A. A. Nugrahaningsih, Wahyu Tri Widayati, Srikanth Karnati, Dwi Liliek Kusindarta
Background: Alzheimer's disease (AD) is a neurodegenerative condition, and the number of cases of AD is projected to increase each year. Developing an AD animal model has a major impact on studying the pathology of the disease and on developing therapies and treatments. Aim: This study aimed to create an AD animal model using C3H mice by administering trimethyltin (TMT) via intraperitoneal injection. Hematological analysis, pathology, protein biomarkers, and behavioral assessments supported the findings. Methods: In this experiment, two groups were included: a non-treated group (normal mouse) and a treatment group (AD animal model). Each group consisted of four male C3H mice aged 8 weeks. The treatment group was intraperitoneally injected 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, proteomic profiling was used to analyze protein biomarkers associated with AD via liquid chromatography-high-resolution mass spectrometry. Behavioral analysis was conducted using the radial arm maze. Results: Hematological analysis revealed an increase in hematocrit, mean corpuscular volume, leucocytes, and neutrophil levels, whereas other parameters remained within the normal range. Histopathological analysis revealed neuronal loss and structural alterations in the pyramidal cell layers of the CA1 and CA3, the presence of inflammation, and neurofibrillary tangles. Proteomic analysis identified several protein biomarkers related to AD in the AD animal model, including amyloid beta, tau protein, apolipoprotein E, and Triggering Receptor Expressed on Myeloid cells. Behavioral analysis demonstrated significant cognitive and memory declines in AD animal models compared with non-treated animals. Conclusion: The intraperitoneal administration of TMT in C3H mice effectively induces pathological changes in the brain that are related to AD. 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 AD, as well as testing new therapies. © 2025, Faculty of Veterinary Medicine, University of Tripoli. All rights reserved.
Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia; Department of Pharmacology, Faculty of Veterinary Medicine, Brawijaya University, Malang, Indonesia; Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia; Regional General Hospital of Karanganyar Regency, Karanganyar, Indonesia; Institute of Anatomy and Cell Biology, Julius Maximillian University, Wuerzburg, Germany
