Aluminum chloride impaired spatial memory, but not senile plaques formation in the rat model of Alzheimer’s disease

Muhammad Ihwan Narwanto*  -  Department of Anatomy, Faculty of Medicine, University of Jember, Jember, Indonesia
Masruroh Rahayu  -  Department of Neurology, Faculty of Medicine, University of Brawijaya, Malang, Indonesia
Setyawati Soeharto  -  Department of Pharmacology, Faculty of Medicine, University of Brawijaya, Malang, Indonesia
Nurdiana Nurdiana  -  Department of Pharmacology, Faculty of Medicine, University of Brawijaya, Malang, Indonesia

(*) Corresponding Author
DOI: 10.30659/sainsmed.v13i1.18102

Aluminum compounds can be easily found in the environment. Aluminum contamination is the environmental factor as one of the risk factors for Alzheimer's disease (AD). In the animal model, aluminum chloride (AlCl3) induces inflammation and oxidative stress. Inflammation and oxidative stress are important pathogenesis pathways in the AD. This study was conducted to determine whether AlCl3 can impair spatial memory and induce senile plaques formation. A total of 24 young adult Wistar rats were used in this study. The rats were divided into four groups; one control group and three AlCl3 treated groups with doses of 150 mg/kg, 300 mg/kg, and 600 mg/kg, respectively for 8 weeks. The spatial memory test was measured using Morris water maze and the histopathology was done by identification of senile plaques formation in the hippocampal tissue. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey's test for multiple comparisons. The level of statistical significance was set at a p value < 0.05. This study showed that there are significant differences (p<0,05) between the control group and all the AlCl3 treatment groups in the memory test, however, there is no change in the senile plaque’s expression in all groups. Administration of AlCl3 for 8 weeks can cause the impaired of spatial memory without senile plaques formation.

Keywords: aluminum chloride; spatial memory; senile plaques; Alzheimer’s disease

  1. Agostinho, P., Cunha, R. and Oliveira, C. (2010). Neuroinflammation, Oxidative Stress and the Pathogenesis of Alzheimer ’ s Disease, Current Pharmacutical Design, 2010;16(25):2766-78. doi: 10.2174/138161210793176572
  2. Aguilar, F., Autrup, H., Barlow, S., Castle, L., Crebelli, R., Dekant, W. et al. (2008). Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials on a request from European Commission on Safety of aluminium from dietary intake. EFSA Journal, 754; 6 (7): 1–122. https://doi.org/10.2903/j.efsa.2008.754
  3. Baydar, T., Papp, A., Aydin, A., Nagymajtenyi, L., Schulz, H., Isimer, A. et al. (2003). Accumulation of aluminum in rat brain. Biological Trace Element Research, 92(3): 231–244. http://dx.doi.org/10.1385/BTER:92:3:231.
  4. Bromley-Brits, K., Deng, Y. and Song, W. (2011). Morris Water Maze test for learning and memory deficits in Alzheimer’s disease model mice. Journal of Visualized Experiments, (53): 2–6. doi: 10.3791/2920.
  5. Cao, Z., Yang, X., Zhang, H., Wang, H., Huang, W., Xu, F. et al. (2016). Aluminum chloride induces neuroinflammation, loss of neuronal dendritic spine and cognition impairment in developing rat. Chemosphere. Elsevier Ltd, 151: 289–295. doi: 10.1016/j.chemosphere.2016.02.092.
  6. Chen, S. M., Fan, C. C., Chiue, M. S., Chou, C., Chen, J. H. and Hseu, R. S. (2013). Hemodynamic and neuropathological analysis in rats with aluminum trichloride-induced Alzheimer’s disease. PLoS ONE, 8(12): 1–11. doi: 10.1371/journal.pone.0082561.
  7. Deture, M. A. and Dickson, D. W. (2019). The neuropathological diagnosis of Alzheimer’s disease. Molecular Neurodegeneration. 14(1): 1–18. doi: 10.1186/s13024-019-0333-5.
  8. Jayakar, J. P. and Huang, J. (2010). Diagnostic review Alzheimer’s disease : A review of diagnostic criteria. University of Western Ontario Medical Journal, 79(2): 7–9.
  9. Kawahara, M. and Kato-Negishi, M. (2011). Link between aluminum and the pathogenesis of Alzheimer’s disease: The integration of the aluminum and amyloid cascade hypotheses. International Journal of Alzheimer’s Disease, 2011. doi: 10.4061/2011/276393.
  10. Killin, L. O. J., Starr, J. M., Shiue, I. J. and Russ, T. C. (2016). Environmental risk factors for dementia: a systematic review’, BMC Geriatrics. BMC Geriatrics, 16(1): 1–28. doi: 10.1186/s12877-016-0342-y.
  11. Lee, J.-E. and Han, P.-L. (2013). An Update of Animal Models of Alzheimer Disease with a Reevaluation of Plaque Depositions. Experimental Neurobiology, 22(2): 84–95. doi: 10.5607/en.2013.22.2.84.
  12. Lin, W. T., Chen, R. C., Lu, W. W., Liu, S. H. and Yang, F.Y. (2015). Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer’s disease rat model. Scientific Reports, 5: 1–7. doi: 10.1038/srep09671.
  13. Massaad, C. A. and Klann, E. (2011). Reactive oxygen species in the regulation of synaptic plasticity and memory’. Antioxidants and Redox Signaling, 14(10): 2013–2054. doi: 10.1089/ars.2010.3208.
  14. Nobakht, M., Hoseini, S. M., Mortazavi, P., Sohrabi, I., Esmaeilzade, B. and Rooshandel, N. R. (2011) Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer’s disease. Iranian Biomedical Journal, 15(1–2): 51–58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639737/
  15. Promyo, K., Igbal, F., Chaidee, N. and Chetsawang B. (2020). Aluminum chloride-induced amyloid β accumulation and endoplasmic reticulum stress in rat brain are averted by melatonin. Food and Chemical Toxicology. Elsevier Ltd, 146 (August). doi: 10.1016/j.fct.2020.111829.
  16. Rajamohamedsait, H. B. and Sigurdsson, E. M. (2012). Histological staining of amyloid and pre-amyloid peptides and proteins in mouse tissue. Methods in Molecular Biology, 849, pp. 411–424. doi: 10.1007/978-1-61779-551-0_28.
  17. Rondeau, V., Jacqmin-Gadda, H., Commenges, D., Helmer, C. and Dartigues, J.F. (2009). Aluminum and silica in drinking water and the risk of Alzheimer’s disease or cognitive decline: Findings from 15-year follow-up of the PAQUID cohort’. American Journal of Epidemiology, 169(4): 489–496. doi: 10.1093/aje/kwn348.
  18. Wall, A. M., Mukandala, G., Greig, N. H., Sciences, B. and Branch, G. (2016). HHS Public Access, 93(5), pp. 815–829. doi: 10.1002/jnr.23540.Tumor.
  19. Wenk, G. L., Mcgann, K., Hauss-Wegrzyniak, B. and Rosi, S. (2003). The toxicity of tumor necrosis factor-α upon cholinergic neurons within the nucleus basalis and the role of norepinephrine in the regulation of inflammation: Implications for Alzheimer’s disease. Neuroscience, 121(3): 719–729. doi: 10.1016/S0306-4522(03)00545-1.
  20. Yuan, C. Y., Lee, Y. J. and Hsu, G. S. W. (2012). Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats. Journal of Biomedical Science, 19(1): 1–9. doi: 10.1186/1423-0127-19-51.

Open Access Copyright (c) 2022 Sains Medika: Jurnal Kedokteran dan Kesehatan
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Sains Medika: Jurnal Kedokteran dan Kesehatan
is published by Fakultas Kedokteran Universitas Islam Sultan Agung Semarang, Indonesia.
Jl. Raya Kaligawe Km.4, PO BOX 1054/SM Semarang 50112
Website: https://fkunissula.ac.id/
Email: sainsmedika@unissula.ac.idsainsmedika@unissula.ac.id

ISSN: 2339-093X (Online) | 2085-1545 (Print)
DOI : 10.30659/sainsmed

This work is licensed under a Creative Commons Attribution 4.0 International License

Get a feed by atom here, RRS2 here and OAI Links here

apps