Volume 7, Issue 4 (Journal of Clinical and Basic Research (JCBR) 2023)                   jcbr 2023, 7(4): 15-19 | Back to browse issues page

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Azhir M, Gazmeh S, Elyasi L, Jahanshahi M, Bazrafshan B. The effect of apelin-13 on memory of scopolamine-treated rats and accumulation of amyloid-beta plaques in the hippocampus. jcbr 2023; 7 (4) :15-19
URL: http://jcbr.goums.ac.ir/article-1-412-en.html
1- Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran
2- Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran , lyasy_leila@yahoo.com
3- School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
Abstract:   (200 Views)
Background: Neurodegenerative diseases (NDDs) cause progressive neuronal loss, resulting in morbidity and mortality. Research is continued on treatment strategies that can tackle the disease's pathophysiology and cease its progression. Considering the anti-apoptotic and neuroprotective properties of apelin, we hypothesized that apelin-13 could be a therapeutic solution for Alzheimer's disease and similar NDDs. Therefore, we evaluated its effect on scopolamine-treated rats.
Methods: Male rats (n=40) were assigned to 5 groups of 8. No intervention was considered for the control group. The scopolamine group received stereotaxic surgery and was treated with 3 mg/kg scopolamine intraperitoneally. The treatment groups were treated with scopolamine plus intraventricular injection of apelin-13 (1.25, 2.5, and 5 µg) into the right lateral ventricles for 7 days. For evaluating the memory impairment, the passive avoidance reactions of the animals, except the control group, were assessed 24 hours following the last injection. Regarding histological analysis, Congo red staining of the hippocampal sections was done, and immunoblotting was used to determine apoptotic biochemical markers, including caspase 3, cytochrome C, and congophilic amyloid-beta plaques.
Results: Apelin–13 alleviated scopolamine-related passive avoidance memory impairment and reduced the number of congophilic amyloid-beta plaques in the hippocampus (all P<0.001). It attenuated the decrease in the mean levels of hippocampal apoptotic proteins (caspase 3, cytochrome C) in animals treated with scopolamine (all P<0.05).
Conclusion: The neuroprotective effects of apelin-13 suggest its therapeutic effect on neurodegenerative disorders.
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Article Type: Research | Subject: Neuroscience

1. Wray S. Modelling neurodegenerative disease using brain organoids. Semin Cell Dev Biol. 2021;111:60-6. [View at Publisher] [DOI] [PMID] [Google Scholar]
2. Zhu J, Dou S, Jiang Y, Chen J, Wang C, Cheng B. Apelin-13 protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through inhibiting endoplasmic reticulum stress and promoting autophagy. Brain Res. 2019;1715:203-12. [View at Publisher] [DOI] [PMID] [Google Scholar]
3. Budelier MM, Bateman RJ. Biomarkers of Alzheimer Disease. J Appl Lab Med. 2020;5(1):194-208. [View at Publisher] [DOI] [PMID] [Google Scholar]
4. Chen Z-R, Huang J-B, Yang S-L, Hong F-F. Role of Cholinergic Signaling in Alzheimer's Disease. Molecules. 2022;27(6):1816. [View at Publisher] [DOI] [PMID] [Google Scholar]
5. Tang KS. The cellular and molecular processes associated with scopolamine-induced memory deficit: A model of Alzheimer's biomarkers. Life Sci. 2019;233:116695. [View at Publisher] [DOI] [PMID] [Google Scholar]
6. 2020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020;16(3):391-460. [View at Publisher] [DOI] [PMID]
7. Terranova JI, Ogawa SK, Kitamura T. Adult hippocampal neurogenesis for systems consolidation of memory. Behav Brain Res. 2019;372:112035. [View at Publisher] [DOI] [PMID] [Google Scholar]
8. Puzzo D, Fiorito J, Purgatorio R, Gulisano W, Palmeri A, Arancio O, et al. Chapter 1 - Molecular Mechanisms of Learning and Memory**The authors declare no competing financial interests. In: Lazarov O, Tesco G, editors. Genes, Environment and Alzheimer's Disease. San Diego: Academic Press; 2016. p. 1-27. [View at Publisher] [DOI] [Google Scholar]
9. Kumar A, Singh A, Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 2015;67(2):195-203. [View at Publisher] [DOI] [PMID] [Google Scholar]
10. Ulep MG, Saraon SK, McLea S. Alzheimer Disease. The Journal for Nurse Practitioners. 2018;14(3):129-35. [View at Publisher] [DOI] [Google Scholar]
11. Derby CA. Trends in the public health significance, definitions of disease, and implications for prevention of Alzheimer's disease. Curr Epidemiol Rep. 2020;7(2):68-76. [View at Publisher] [DOI] [PMID] [Google Scholar]
12. Esposito Z, Belli L, Toniolo S, Sancesario G, Bianconi C, Martorana A. Amyloid β, glutamate, excitotoxicity in Alzheimer's disease: are we on the right track? CNS Neurosci Ther. 2013;19(8):549-55. [View at Publisher] [DOI] [PMID] [Google Scholar]
13. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer's disease. Mol Neurodegener. 2019;14(1):32. [View at Publisher] [DOI] [PMID] [Google Scholar]
14. Roth KA. Caspases, apoptosis, and Alzheimer disease: causation, correlation, and confusion. J Neuropathol Exp Neurol. 2001;60(9):829-38. [View at Publisher] [DOI] [PMID] [Google Scholar]
15. Onyango IG, Jauregui GV, Čarná M, Bennett Jr JP, Stokin GB. Neuroinflammation in Alzheimer's disease. Biomedicines. 2021;9(5):524. [View at Publisher] [DOI] [PMID] [Google Scholar]
16. Masoumi J, Abbasloui M, Parvan R, Mohammadnejad D, Pavon-Djavid G, Barzegari A, et al. Apelin, a promising target for Alzheimer disease prevention and treatment. Neuropeptides. 2018;70:76-86. [View at Publisher] [DOI] [PMID] [Google Scholar]
17. Aminyavari S, Zahmatkesh M, Khodagholi F, Sanati M. Anxiolytic impact of Apelin-13 in a rat model of Alzheimer's disease: Involvement of glucocorticoid receptor and FKBP5. Peptides. 2019;118:170102. [View at Publisher] [DOI] [PMID] [Google Scholar]
18. Lv SY, Chen WD, Wang YD. The Apelin/APJ System in Psychosis and Neuropathy. Front Pharmacol. 2020;11:320. [View at Publisher] [DOI] [PMID] [Google Scholar]
19. Zhou JX, Shuai NN, Wang B, Jin X, Kuang X, Tian SW. Neuroprotective gain of Apelin/APJ system. Neuropeptides. 2021;87:102131. [View at Publisher] [DOI] [PMID] [Google Scholar]
20. Zhang Y, Jiang W, Sun W, Guo W, Xia B, Shen X, et al. Neuroprotective Roles of Apelin-13 in Neurological Diseases. Neurochem Res. 2023:48(6):1648-62. [View at Publisher] [DOI] [PMID] [Google Scholar]
21. Xin Q, Cheng B, Pan Y, Liu H, Chen J, Bai B. Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation. Peptides. 2015;63:55-62. [View at Publisher] [DOI] [PMID] [Google Scholar]
22. Zhu J, Gao W, Shan X, Wang C, Wang H, Shao Z, et al. Apelin-36 mediates neuroprotective effects by regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson's disease model mice. Brain Res. 2020;1726:146493. [View at Publisher] [DOI] [PMID] [Google Scholar]
23. Wan T, Fu M, Jiang Y, Jiang W, Li P, Zhou S. Research Progress on Mechanism of Neuroprotective Roles of Apelin-13 in Prevention and Treatment of Alzheimer's Disease. Neurochem Res. 2022;47(2):205-17. [View at Publisher] [DOI] [PMID] [Google Scholar]
24. Antushevich H, Wójcik M. Review: Apelin in disease. Clin Chim Acta. 2018;483:241-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
25. Yildiz Z, Eren N, Orcun A, Münevver Gokyigit F, Turgay F, Gündogdu Celebi L. Serum apelin-13 levels and total oxidant/antioxidant status of patients with Alzheimer's disease. Aging Med (Milton). 2021;4(3):201-5. [View at Publisher] [DOI] [PMID] [Google Scholar]
26. Wan T, Fu M, Jiang Y, Jiang W, Li P, Zhou S. Research progress on mechanism of neuroprotective roles of Apelin-13 in prevention and treatment of Alzheimer's disease. Neurochem Res. 2022:47(2):205-17. [View at Publisher] [DOI] [PMID] [Google Scholar]
27. Luo H, Xiang Y, Qu X, Liu H, Liu C, Li G, et al. Apelin-13 suppresses neuroinflammation against cognitive deficit in a streptozotocin-induced rat model of Alzheimer's disease through activation of BDNF-TrkB signaling pathway. Front Pharmacol. 2019;10:395. [View at Publisher] [DOI] [PMID] [Google Scholar]
28. Paul J. Chapter 5 - Experimental Medicine Approaches in CNS Drug Development. In: Nomikos GG, Feltner DE, editors. Handbook of Behavioral Neuroscience.US: Elsevier; 2019. Vol 29. p 63-80. [View at Publisher] [DOI] [Google Scholar]
29. Haghparast E, Esmaeili-Mahani S, Abbasnejad M, Sheibani V. Apelin-13 ameliorates cognitive impairments in 6-hydroxydopamine-induced substantia nigra lesion in rats. Neuropeptides. 2018;68:28-35. [View at Publisher] [DOI] [PMID] [Google Scholar]
30. Folch J, Petrov D, Ettcheto M, Abad S, Sánchez-López E, García ML, et al. Current Research Therapeutic Strategies for Alzheimer's Disease Treatment. Neural Plast. 2016;2016:8501693. [View at Publisher] [DOI] [PMID] [Google Scholar]
31. Aminyavari S, Zahmatkesh M, Farahmandfar M, Khodagholi F, Dargahi L, Zarrindast MR. Protective role of Apelin-13 on amyloid β25-35-induced memory deficit; Involvement of autophagy and apoptosis process. Prog Neuropsychopharmacol Biol Psychiatry. 2019;89:322-34. [View at Publisher] [DOI] [PMID] [Google Scholar]
32. Eren N, Den Z, Yildiz Z, Go N, Gu L, Karabiyik T. P200-levels of Apelin-13 and total oxidant/antioxidant status in sera of Alzheimer patients. Turkish Journal of Biochemistry/Turk Biyokimya Dergisi. 2012;37(S1):341. [View at Publisher] [Google Scholar]
33. Luo H, Han L, Xu J. Apelin/APJ system: a novel promising target for neurodegenerative diseases. J Cell Physiol. 2020;235(2):638-57. [View at Publisher] [DOI] [PMID] [Google Scholar]
34. Samandari-Bahraseman MR, Elyasi L. Apelin-13 protects human neuroblastoma SH-SY5Y cells against amyloid-beta induced neurotoxicity: Involvement of anti oxidant and anti apoptotic properties. J Basic Clin Physiol Pharmacol. 2021;33(5):599-605. [View at Publisher] [DOI] [PMID] [Google Scholar]
35. Chen P, Wang Y, Chen L, Song N, Xie J. Apelin-13 protects dopaminergic neurons against rotenone-induced neurotoxicity through the AMPK/mTOR/ULK-1 mediated autophagy activation. Int J Mol Sci. 2020;21(21):8376. [View at Publisher] [DOI] [PMID] [Google Scholar]
36. Niknazar S, Abbaszadeh H-A, Peyvandi H, Rezaei O, Forooghirad H, Khoshsirat S, et al. Protective effect of [Pyr1]-apelin-13 on oxidative stress-induced apoptosis in hair cell-like cells derived from bone marrow mesenchymal stem cells. Eur J Pharmacol. 2019;853:25-32. [View at Publisher] [DOI] [PMID] [Google Scholar]
37. Khaledi S, Ahmadi S. Amyloid Beta and Tau: from Physiology to Pathology in Alzheimer's Disease. The Neuroscience Journal of Shefaye Khatam. 2016;4(4):67-88. [View at Publisher] [DOI] [Google Scholar]
38. Respekta N, Pich K, Dawid M, Mlyczyńska E, Kurowska P, Rak A. The Apelinergic System: Apelin, ELABELA, and APJ Action on Cell Apoptosis: Anti-Apoptotic or Pro-Apoptotic Effect? Cells. 2022;12(1):150. [View at Publisher] [DOI] [PMID] [Google Scholar]
39. Zeng X, Yu SP, Taylor T, Ogle M, Wei L. Protective effect of apelin on cultured rat bone marrow mesenchymal stem cells against apoptosis. Stem Cell Res. 2012;8(3):357-67. [View at Publisher] [DOI] [PMID] [Google Scholar]
40. Wang D, Wang Y, Shan M, Chen J, Wang H, Sun B, et al. Apelin receptor homodimer inhibits apoptosis in vascular dementia. Exp Cell Res. 2021;407(1):112739. [View at Publisher] [DOI] [PMID] [Google Scholar]
41. Xu W, Li T, Gao L, Zheng J, Yan J, Zhang J, et al. Apelin-13/APJ system attenuates early brain injury via suppression of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation and oxidative stress in a AMPK-dependent manner after subarachnoid hemorrhage in rats. J Neuroinflammation. 2019;16(1):247. [View at Publisher] [DOI] [PMID] [Google Scholar]
42. Liu Y, Zhang T, Wang Y, Wu P, Li Y, Wang C, et al. Apelin-13 attenuates early brain injury following subarachnoid hemorrhage via suppressing neuronal apoptosis through the GLP-1R/PI3K/Akt signaling. Biochem Biophys Res commun. 2019;513(1):105-11. [View at Publisher] [DOI] [PMID] [Google Scholar]
43. Zhang L, Li F, Su X, Li Y, Wang Y, Fang R, et al. Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction. Exp Mol Med. 2019;51(7):1-12. [View at Publisher] [DOI] [PMID] [Google Scholar]
44. Chen WN, Yeong KY. Scopolamine, a Toxin-Induced Experimental Model, Used for Research in Alzheimer's Disease. CNS Neurol Disord Drug Targets. 2020;19(2):85-93. [View at Publisher] [DOI] [PMID] [Google Scholar]
45. Safar MM, Arab HH, Rizk SM, El-Maraghy SA. Bone Marrow-Derived Endothelial Progenitor Cells Protect Against Scopolamine-Induced Alzheimer-Like Pathological Aberrations. Mol Neurobiol. 2016;53(3):1403-18. [View at Publisher] [DOI] [PMID] [Google Scholar]
46. Bajo R, Pusil S, López ME, Canuet L, Pereda E, Osipova D, et al. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer's disease. Sci Rep. 2015;5(1):9748. [View at Publisher] [DOI] [PMID] [Google Scholar]
47. Gazmeh S, Azhir M, Elyasi L, Jahanshahi M, Nikmahzar E, Jameie SB. Apelin-13 protects against memory impairment and neuronal loss, Induced by Scopolamine in male rats. Metab Brain Dis. 2022;37(3):701-9. [View at Publisher] [DOI] [PMID] [Google Scholar]

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