Characteristics of streptozotocin-induced and okadaic acid-induced models of Alzheimer's disease
Keywords:
Dementia, Okadaic Acid, Acids, Streptozotocin, Alzheimer's disease.
Abstract
alzheimer's disease is the main cause of dementia in people over the age of 65, which affects millions of patients worldwide. Since the prevalence of this pathology increases significantly with the increase in life expectancy, the societal consequences of Alzheimer's disease will be dire if no effective therapy is developed in the near future. Fundamental experimental work is a mandatory and necessary stage of preclinical research for the safe and effective development of new approaches to the treatment of dementia as part of clinical trials in the future. Streptozotocin is a natural chemical obtained from Streptomyces achromogenes, primarily classified as an antibiotic, the introduction of which leads to the activation of oxidative stress and damage to the myelin sheath. This chemical compound promotes the accumulation of characteristic abnormal proteins, called β-amyloid and tau protein, which leads to imitation of neuropathological, behavioral, metabolic and molecular symptoms that resemble human Alzheimer's disease. Okadaic acid is a C38 fatty acid polyester phycotoxin, which is a powerful and selective inhibitor of serine/threonine phosphatases: PP-1c, PP1, PP2A and PP2B, which leads to a decrease in dephosphorylation of phosphorylated tau protein and, accordingly, to hyperphosphorylation of tau protein. Hyperphosphorylation of tau protein is responsible for the deposition of neurofibrillary tangles in vivo and in vitro, which ultimately causes synaptic dysfunction and neuronal death. In addition, okadaic acid activates kinases that regulate tau protein phosphorylation: GSK3β, CDK5, MAPK, ERK1/2, AMPK. The activation of kinases significantly contributes to the phosphorylation of tau protein. Okadain administration is also reported to significantly activate the expression of BACE1, one of the key enzymes in the amyloidogenic cascade. The mechanisms of molecular and morphological changes of the Alzheimer's type in the brain of experimental animals when streptozotocin and okadaic acid are administered are similar in many respects. These include induction and activation of neurodegeneration, apoptosis and necrosis of neurons, development of oxidative stress and inhibition of antioxidant systems, deficiency of neurotransmitters and mitochondrial dysfunction, etc. Both proposed toxins effectively contribute to the simulation of dementia of the Alzheimer's type in the experiment.
References
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Bajaj, S., Zameer, S., Jain, S., Yadav, V., & Vohora, D. (2022). Effect of the MAGL/FAAH dual inhibitor JZL-195 on streptozotocin-induced Alzheimer’s disease-like sporadic dementia in mice with an emphasis on Aβ, HSP-70, neuroinflammation, and oxidative stress. ACS chemical neuroscience, 13(7), 920-932.
Barai, P., Raval, N., Acharya, S., & Acharya, N. (2018). Bergenia ciliata ameliorates streptozotocin-induced spatial memory deficits through dual cholinesterase inhibition and attenuation of oxidative stress in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 102, 966–980. https://doi.org/10.1016/j.biopha.2018.03.115
Bhuvanendran, S., Kumari, Y., Othman, I., & Shaikh, M. F. (2018). Amelioration of cognitive deficit by embelin in a scopolamine-induced Alzheimer’s disease-like condition in a rat model. Frontiers in Pharmacology, 9, 374992.
Çakır, M., Yüksel, F., Mustafa Özkut, M., Durhan, M., Kaymak, E., Tekin, S., & Çiğremiş, Y. (2023a). Neuroprotective effect of transient receptor potential Vanilloid 1 agonist capsaicin in Alzheimer's disease model induced with okadaic acid. International immunopharmacology, 118, 109925. https://doi.org/10.1016/j.intimp.2023.109925
Çakır, M., Yüksel, F., Mustafa Özkut, M., Durhan, M., Kaymak, E., Tekin, S., & Çiğremiş, Y. (2023b). Neuroprotective effect of transient receptor potential Vanilloid 1 agonist capsaicin in Alzheimer's disease model induced with okadaic acid. International immunopharmacology, 118, 109925. https://doi.org/10.1016/j.intimp.2023.109925
Cao, Q., Tan, C. C., Xu, W., Hu, H., Cao, X. P., Dong, Q., Tan, L., & Yu, J. T. (2020). The Prevalence of Dementia: A Systematic Review and Meta-Analysis. Journal of Alzheimer's disease : JAD, 73(3), 1157–1166. https://doi.org/10.3233/JAD-191092
Cardoso, S., Carvalho, C., Correia, S. C., & Moreira, P. I. (2024). Protective effects of 2,4-dinitrophenol in okadaic acid-induced cellular model of Alzheimer's disease. Biochimica et biophysica acta. Molecular basis of disease, 1870(6), 167222. Advance online publication. https://doi.org/10.1016/j.bbadis.2024.167222
Chou, C. H., & Yang, C. R. (2021). Neuroprotective Studies of Evodiamine in an Okadaic Acid-Induced Neurotoxicity. International journal of molecular sciences, 22(10), 5347. https://doi.org/10.3390/ijms22105347
Chu, J., Wang, J., Cui, L., Liu, S., An, N., Han, J., ... & Yang, J. (2021). Pseudoginsenoside-F11 ameliorates okadiac acid-induced learning and memory impairment in rats via modulating protein phosphatase 2A. Mechanisms of Ageing and Development, 197, 111496.
Cui, J., Meng, Y. H., Wang, Z. W., Wang, J., Shi, D. F., & Liu, D. (2023). Ganoderic Acids A and B Reduce Okadaic Acid-Induced Neurotoxicity in PC12 Cells by Inhibiting Tau Hyperphosphorylation. Biomedical and environmental sciences : BES, 36(1), 103–108. https://doi.org/10.3967/bes2023.011
Dashniani, M. G., Chighladze, M. R., Solomonia, R. O., Burjanadze, M. A., Kandashvili, M., Chkhikvishvili, N. C., Beselia, G. V., & Kruashvili, L. B. (2020). Memantine treatment prevents okadaic acid induced neurotoxicity at the systemic and molecular levels. Neuroreport, 31(4), 281–286. https://doi.org/10.1097/WNR.0000000000001375
Dos Santos, J. P. A., Vizuete, A. F., & Gonçalves, C. A. (2020). Calcineurin-Mediated Hippocampal Inflammatory Alterations in Streptozotocin-Induced Model of Dementia. Molecular neurobiology, 57(1), 502–512. https://doi.org/10.1007/s12035-019-01718-2
Dubey, R., Sathiyanarayanan, L., Sankaran, S., & Arulmozhi, S. (2023). Nootropic effect of Indian Royal Jelly against okadaic acid induced rat model of Alzheimer's disease: Inhibition of neuroinflammation and acetylcholineesterase. Journal of traditional and complementary medicine, 14(3), 300–311. https://doi.org/10.1016/j.jtcme.2023.11.005
Fanoudi, S., Hosseini, M., Alavi, M. S., Boroushaki, M. T., Hosseini, A., & Sadeghnia, H. R. (2018). Everolimus, a mammalian target of rapamycin inhibitor, ameliorated streptozotocin-induced learning and memory deficits via neurochemical alterations in male rats. EXCLI journal, 17, 999–1017. https://doi.org/10.17179/excli2018-1626
Foidl, B. M., & Humpel, C. (2018). Differential Hyperphosphorylation of Tau-S199, -T231 and -S396 in Organotypic Brain Slices of Alzheimer Mice. A Model to Study Early Tau Hyperphosphorylation Using Okadaic Acid. Frontiers in aging neuroscience, 10, 113. https://doi.org/10.3389/fnagi.2018.00113
Gao, Y., Wang, X. Q., Ma, S., Dong, Y. C., & Shang, Y. Z. (2021). Flavonoids from stem and leaf of Scutellaria baicalensis georgi inhibit the phosphorylation on multi-sites of tau protein induced by okadaic acid and the regulative mechanism of protein kinases in rats. Combinatorial Chemistry & High Throughput Screening, 24(7), 1126-1136.
Ghimire, K., Zaric, J., Alday-Parejo, B., Seebach, J., Bousquenaud, M., Stalin, J., Bieler, G., Schnittler, H. J., & Rüegg, C. (2019). MAGI1 Mediates eNOS Activation and NO Production in Endothelial Cells in Response to Fluid Shear Stress. Cells, 8(5), 388. https://doi.org/10.3390/cells8050388
Grieb, P. (2016). Intracerebroventricular streptozotocin injections as a model of Alzheimer’s disease: in search of a relevant mechanism. Molecular neurobiology, 53, 1741-1752.
Gupta, T., Singh, V., Hefnawy, M., Alanazi, M. M., Alsuwayt, B., Kabra, A., Kumar, A., Pasricha, C., & Singh, R. (2023). Ameliorating the Role of Aripiprazole in Memory Deficits Induced by Intracerebroventricular Streptozotocin-Induced Dementia of Alzheimer's Type. ACS omega, 8(28), 25295–25302. https://doi.org/10.1021/acsomega.3c02550
Hampel, H., Mesulam, M. M., Cuello, A. C., Khachaturian, A. S., Vergallo, A., Farlow, M. R., Snyder, P. J., Giacobini, E., & Khachaturian, Z. S. (2019). Revisiting the Cholinergic Hypothesis in Alzheimer's Disease: Emerging Evidence from Translational and Clinical Research. The journal of prevention of Alzheimer's disease, 6(1), 2–15. https://doi.org/10.14283/jpad.2018.43
https://en.wikipedia.org/wiki/Phycotoxin
Huang, L., Zhong, X., Xu, Y., Deng, M., & Zhou, Z. (2023). β-asarone Protects p-tau from Okadaic Acid in PC12 Cells by Activating PP2A and Involving Akt/mTOR/Beclin-1 Pathway. Pharmacognosy Magazine, 19(3), 727-735.
Jiang, W., Luo, T., Li, S., Zhou, Y., Shen, X. Y., He, F., Xu, J., & Wang, H. Q. (2016). Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons. PloS one, 11(4), e0152371. https://doi.org/10.1371/journal.pone.0152371
Kamat, P. K., Tota, S., Rai, S., Shukla, R., Ali, S., Najmi, A. K., & Nath, C. (2012). Okadaic acid induced neurotoxicity leads to central cholinergic dysfunction in rats. European journal of pharmacology, 690(1-3), 90–98. https://doi.org/10.1016/j.ejphar.2012.06.006
Kaur, R., Randhawa, K., Kaur, S., & Shri, R. (2020). Allium cepa fraction attenuates STZ-induced dementia via cholinesterase inhibition and amelioration of oxidative stress in mice. Journal of basic and clinical physiology and pharmacology, 31(3).
Lin, M., Li, P., Liu, W., Niu, T., & Huang, L. (2022). Germacrone alleviates okadaic acid-induced neurotoxicity in PC12 cells via M1 muscarinic receptor-mediated Galphaq (Gq)/phospholipase C beta (PLCβ)/protein kinase C (PKC) signaling. Bioengineered, 13(3), 4898-4910.
Nazari-Serenjeh, M., Baluchnejadmojarad, T., Hatami-Morassa, M., Fahanik-Babaei, J., Mehrabi, S., Tashakori-Miyanroudi, M., Ramazi, S., Mohamadi-Zarch, S. M., Nourabadi, D., & Roghani, M. (2024). Kolaviron neuroprotective effect against okadaic acid-provoked cognitive impairment. Heliyon, 10(3), e25564. https://doi.org/10.1016/j.heliyon.2024.e25564
Palleria, C., Leo, A., Andreozzi, F., Citraro, R., Iannone, M., Spiga, R., Sesti, G., Constanti, A., De Sarro, G., Arturi, F., & Russo, E. (2017). Liraglutide prevents cognitive decline in a rat model of streptozotocin-induced diabetes independently from its peripheral metabolic effects. Behavioural brain research, 321, 157–169. https://doi.org/10.1016/j.bbr.2017.01.004
Pan, Y., Zhang, Y., Liu, N., Lu, W., Yang, J., Li, Y., Liu, Z., Wei, Y., Lou, Y., & Kong, J. (2021). Vitamin D Attenuates Alzheimer-like Pathology Induced by Okadaic Acid. ACS chemical neuroscience, 12(8), 1343–1350. https://doi.org/10.1021/acschemneuro.0c00812
Qi, C. C., Chen, X. X., Gao, X. R., Xu, J. X., Liu, S., & Ge, J. F. (2021). Impaired Learning and Memory Ability Induced by a Bilaterally Hippocampal Injection of Streptozotocin in Mice: Involved With the Adaptive Changes of Synaptic Plasticity. Frontiers in aging neuroscience, 13, 633495. https://doi.org/10.3389/fnagi.2021.633495
QIAN, H. Y., XIAO, Y. S., HOU, J. H., JIANG, J. L., ZHANG, Q., ZUO, A. R., & GAO, M. (2021). Effect of Huangjingwan on expressions of Wnt/β-catenin signal pathway-associated proteins in hippocampus of mice with Alzheimer's disease induced by D-galactose and okadaic acid with learning and memory disorders. Chinese Journal of Experimental Traditional Medical Formulae, 63-71.
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Published
2024-08-12
How to Cite
1.
Nevmerzhytska N, Yaremenko L. Characteristics of streptozotocin-induced and okadaic acid-induced models of Alzheimer’s disease. USMYJ [Internet]. 2024Aug.12 [cited 2026May20];147(2):98-104. Available from: https://mmj.nmuofficial.com/index.php/journal/article/view/416
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THE ARTICLES ARE "TISSUE REACTIONS IN THE NORM, EXPERIMENT AND CLINIC"
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