Dental Pulp Stem Cells Transplantation Improves Passive Avoidance Memory and Neuroinflammation in Trimethyltin-Induced Alzheimer’s Disease Rat Model

  • Samira Malekzadeh 1. Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran 2. Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran http://orcid.org/0000-0003-0125-7839
  • Mohammad Amin Edalatmanesh 2. Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
  • Davood Mehrabani 3. Stem Cell and Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Mehrdad Shariati 4. Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran
Keywords: Stem Cells, Memory, Cognitive Dysfunction, Trimethyltin, Alzheimer Disease

Abstract

Background: According to the increasing incidence of Alzheimer’s disease (AD), this study aimed to investigate the effect of dental pulp stem cells (DPSCs) transplantation on passive avoidance memory and neuroinflammation in trimethyltin (TMT)-induced AD rat model. Materials and Methods: In this experimental study, 18 male Wistar rats were randomly divided into three groups: the control that rats received 8 mg/kg TMT plus 0.5 ml phosphate buffered saline (PBS) and TMT+DPSCs (TMT + 1×106 cells/ml DPSC in 0.5 ml PBS) groups. Then, after one month, passive avoidance test was performed. Also measured the Nuclear Factor Kappa-β (NF-Kβ) serum level and the percentage of damaged neurons in the hippocampus were determined. Results: DPSCs transplantation showed significantly increased step-through latency to the dark compartment in comparison with control and TMT+PBS groups in 24 hours after shock. Also, time spent in the dark compartment of TMT+DPSCs significantly decreased compared to control and TMT+PBS groups in 24 and 48 hours after shock (P<0.05). Furthermore, DPSCs transplantation significantly decreased the NF-Kβ serum level and percentage of damaged pyramidal neurons of CA1 compared with TMT+PBS (P<0.05). Conclusion: DPSCs transplantation improved memory and learning, regulated NF-Kβ serum level, and decreased damage neurons of CA1 hippocampus in TMT-induced AD rat model.

References

Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD. Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2009;106(34):14670-5.

https://doi.org/10.1073/pnas.0903563106

PMid:19667196 PMCid:PMC2732886

Kang JY, Park SK, Guo TJ, Ha JS, Lee DS, Kim JM, et al. Reversal of trimethyltin-induced learning and memory deficits by 3, 5-dicaffeoylquinic acid. Oxid Med Cell Longev. 2016;2016:6981595.

https://doi.org/10.1155/2016/6981595

PMid:28105250 PMCid:PMC5221408

Dyer RS, Walsh TJ, Wonderlin WF, Bercegeay M. The trimethyltin syndrome in rats. Neurobehav Toxicol Teratol. 1982;4(2):127-33.

Ueda T, Inden M, Ito T, Kurita H, Hozumi I. Characteristics and therapeutic potential of dental pulp stem cells on neurodegenerative diseases. Front Neurosci. 2020;14:407.

https://doi.org/10.3389/fnins.2020.00407

PMid:32457568 PMCid:PMC7222959

Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000;97(25):13625-30.

https://doi.org/10.1073/pnas.240309797

PMid:11087820 PMCid:PMC17626

Ponnaiyan D, Jegadeesan V. Comparison of phenotype and differentiation marker gene expression profiles in human dental pulp and bone marrow mesenchymal stem cells. Eur J Dent. 2014;8(3):307-13.

https://doi.org/10.4103/1305-7456.137631

PMid:25202208 PMCid:PMC4144126

Pierdomenico L, Bonsi L, Calvitti M, Rondelli D, Arpinati M, Chirumbolo G, et al. Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation. 2005;80(6):836-42.

https://doi.org/10.1097/01.tp.0000173794.72151.88

PMid:16210973

Nito C, Sowa K, Nakajima M, Sakamoto Y, Suda S, Nishiyama Y, et al. Transplantation of human dental pulp stem cells ameliorates brain damage following acute cerebral ischemia. Biomed Pharmacother. 2018;108:1005-14.

https://doi.org/10.1016/j.biopha.2018.09.084

PMid:30372800

McGinley LM, Kashlan ON, Bruno ES, Chen KS, Hayes JM, Kashlan SR, et al. Human neural stem cell transplantation improves cognition in a murine model of Alzheimer's disease. Sci Rep. 2018;8(1):14776.

https://doi.org/10.1038/s41598-018-33017-6

PMid:30283042 PMCid:PMC6170460

Kim JA, Ha S, Shin KY, Kim S, Lee KJ, Chong YH, et al. Neural stem cell transplantation at critical period improves learning and memory through restoring synaptic impairment in Alzheimer's disease mouse model. Cell Death Dis. 2015;6(6):e1789.

https://doi.org/10.1038/cddis.2015.138

PMid:26086962 PMCid:PMC4669825

Yun HM, Kim HS, Park KR, Shin JM, Kang AR, Il Lee K, et al. Placenta-derived mesenchymal stem cells improve memory dysfunction in an A β 1-42-infused mouse model of Alzheimer's disease. Cell Death Dis. 2013;4(12):e958.

https://doi.org/10.1038/cddis.2013.490

PMid:24336078 PMCid:PMC3877561

Yamasaki TR, Blurton-Jones M, Morrissette DA, Kitazawa M, Oddo S, LaFerla FM. Neural stem cells improve memory in an inducible mouse model of neuronal loss. J Neurosci. 2007;27(44):11925-33.

https://doi.org/10.1523/JNEUROSCI.1627-07.2007

PMid:17978032 PMCid:PMC6673368

Mita T, Furukawa-Hibi Y, Takeuchi H, Hattori H, Yamada K, Hibi H, Yamamoto A. Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer's disease. Behav Brain Res. 2015;293:189-97.

https://doi.org/10.1016/j.bbr.2015.07.043

PMid:26210934

Roghani M, Baluchnejadmojarad T. Chronic Rumex Patientia Seed Feeding Improves Passive Avoidance Learning and Memory in Streptozotocin-Diabetic Rats. Basic and Clinical Neuroscience. 2010; 1(4):53-6.‏

Woodruff ML, Baisden RH. Trimethyltin neurotoxicity in the rat as an analogous model of Alzheimer's disease. In Toxin-induced models of neurological disorders. 1994; 319-35.

https://doi.org/10.1007/978-1-4899-1447-7_12

Martin F, Corrigan FM, Donard OFX, Kelly J, Besson JAO, Horrobin DF. Organotin compounds in trimethyltin-treated rats and in human brain in Alzheimer's Disease. Hum Exp Toxicol. 1997;16(9):512-5.

https://doi.org/10.1177/096032719701600906

PMid:9306138

Zhang XM, Ouyang YJ, Yu BQ, Li W, Yu MY, Li JY, et al. Therapeutic potential of dental pulp stem cell transplantation in a rat model of Alzheimer's disease. Neural Regen Res. 2021;16(5):893-8.

https://doi.org/10.4103/1673-5374.297088

PMid:33229725 PMCid:PMC8178760

Geloso MC, Giannetti S, Cenciarelli C, Budoni M, Casalbore P, Maira G, et al. Transplantation of foetal neural stem cells into the rat hippocampus during trimethyltin-induced neurodegeneration. Neurochem Res. 2007;32(12):2054-61.

https://doi.org/10.1007/s11064-007-9353-6

PMid:17457672

Wang DR, Wang YH, Pan J, Tian WD.‏ Neurotrophic effects of dental pulp stem cells in repair of peripheral nerve after crush injury. World J Stem Cells. 2020;12(10):1196-213.

https://doi.org/10.4252/wjsc.v12.i10.1196

PMid:33178401 PMCid:PMC7596440

Qing Y, Liang Y, Du Q, Fan P, Xu H, Xu Y, et al. Apoptosis induced by Trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-κB and MAPKs signaling pathways. Arch Toxicol. 2013;87(7):1273-85.

https://doi.org/10.1007/s00204-013-1021-9

PMid:23423712

Jha NK, Jha SK, Kar R, Nand P, Swati K, Goswami VK. Nuclear factor‐kappa β as a therapeutic target for Alzheimer's disease. J Neurochem. 2019;150(2):113-37.

https://doi.org/10.1111/jnc.14687

PMid:30802950

Shih RH, Wang CY, Yang CM. NF-kappaB signaling pathways in neurological inflammation: a mini review. Front Mol Neurosci. 2015;8:77.

https://doi.org/10.3389/fnmol.2015.00077

PMid:26733801 PMCid:PMC4683208

Jones SV, Kounatidis I. Nuclear factor-kappa B and Alzheimer disease, unifying genetic and environmental risk factors from cell to humans. Front Immunol. 2017;8:1805.

https://doi.org/10.3389/fimmu.2017.01805

PMid:29312321 PMCid:PMC5732234

Snow WM, Albensi BC. Neuronal gene targets of NF-κB and their dysregulation in Alzheimer's disease. Front Mol Neurosci. 2016;9:118.

https://doi.org/10.3389/fnmol.2016.00118

PMid:27881951 PMCid:PMC5101203

Pouya S, Heidari M, Baghaei K, Aghdaei HA, Moradi A, Namaki S, et al. Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis. Int Immunopharmacol. 2018;54:86-94.

https://doi.org/10.1016/j.intimp.2017.11.001

PMid:29112894

Hossein-Khannazer N, Hashemi SM, Namaki S, Sattari M, Khojasteh A. The effects of dental pulp stem cell conditioned media on the proliferation of peripheral blood mononuclear cells. Immunoregulation. 2020;2(2):69-74.

https://doi.org/10.32598/IMMUNOREGULATION.1.4.187

Hunsaker MR, Rosenberg JS, Kesner RP. The role of the dentate gyrus, CA3a, b, and CA3c for detecting spatial and environmental novelty. Hippocampus. 2008;18(10):1064-73.

https://doi.org/10.1002/hipo.20464

PMid:18651615

Kotani S, Yamauchi T, Teramoto T, Ogura H. Pharmacological evidence of cholinergic involvement in adult hippocampal neurogenesis in rats. Neuroscience. 2006;142(2):505-14.

https://doi.org/10.1016/j.neuroscience.2006.06.035

PMid:16889901

Nikkhah A, Ghahremanitamadon F, Zargooshnia S, Shahidi S, Soleimani AS. Effect of amyloid β-peptide on passive avoidance learning in rats: a behavioral study. Biomed Res Int. 2014;2014:798535.

https://doi.org/10.17795/ajnpp-18664

PMid:25013802 PMCid:PMC4071970

Yamaguchi Y, Kawashima S. Effects of amyloid-β-(25-35) on passive avoidance, radial-arm maze learning and choline acetyltransferase activity in the rat. Eur J Pharmacol. 2001;412(3):265-72.

https://doi.org/10.1016/S0014-2999(01)00730-0

Harkany T, O'mahony S, Kelly JP, Soos K, Törõ I, Penke B, et al. β-Amyloid (Phe (SO3H) 24) 25-35 in rat nucleus basalis induces behavioral dysfunctions, impairs learning and memory and disrupts cortical cholinergic innervation. Behav Brain Res. 1998; 90(2): 133-45.‏

https://doi.org/10.1016/S0166-4328(97)00091-0

Yang Y, Cudaback E, Jorstad NL, Hemingway JF, Hagan CE, Melief EJ, et al. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease. Am J Pathol. 2013; 183(3):905-17.‏

https://doi.org/10.1016/j.ajpath.2013.05.009

PMid:23831297 PMCid:PMC3763765

Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A. 2004; 101(1):284-9.‏

https://doi.org/10.1073/pnas.2635903100

PMid:14688411 PMCid:PMC314177

Esmaeilzade B, Nobakht M, Joghataei MT, Roshandel NR, Rasouli H, Kuchaksaraei AS, et al. Delivery of epidermal neural crest stem cells (EPI-NCSC) to hippocamp in Alzheimer's disease rat model. Iran Biomed J. 2012;16(1):1.‏

Babaei P , Tehrani BS. Effect of BDNF and adipose derived stem cells transplantation on cognitive deficit in Alzheimer model of rats. Journal of Behavioral and Brain Science. 2013;3(1):156.‏

https://doi.org/10.4236/jbbs.2013.31015

Padurariu M, Ciobica A, Mavroudis I, Fotiou D, Baloyannis S. Hippocampal neuronal loss in the CA1 and CA3 areas of Alzheimer's disease patients. Psychiatr Danub. 2012;24(2): 152-8.‏

Liu AKL, Chau TW, Lim EJ, Ahmed I, Chang RCC, Kalaitzakis ME, et al. Hippocampal CA2 Lewy pathology is associated with cholinergic degeneration in Parkinson's disease with cognitive decline. Acta Neuropathol Commun. 2019; 7(1):1-13.‏

https://doi.org/10.1186/s40478-019-0717-3

PMid:31023342 PMCid:PMC6485180

Zhang T, Ke W, Zhou X, Qian Y, Feng S, Wang R, et al. Human neural stem cells reinforce hippocampal synaptic network and rescue cognitive deficits in a mouse model of Alzheimer's disease. Stem cell reports. 2019; 13(6):1022-37.‏

https://doi.org/10.1016/j.stemcr.2019.10.012

PMid:31761676 PMCid:PMC6915849

Eftekharzadeh M, Nobakht M, Alizadeh A, Soleimani M, Hajghasem M, Shargh, BK, et al. The effect of intrathecal delivery of bone marrow stromal cells on hippocampal neurons in rat model of Alzheimer's disease. Iran J Basic Med Sci. 2015;18(5):520-5.

Zhu S, Min D, Zeng J, Ju Y, Liu Y, Chen X. Transplantation of Stem Cells from human exfoliated deciduous teeth decreases cognitive impairment from chronic cerebral ischemia by reducing neuronal apoptosis in rats. Stem Cells Int. 2020;2020:6393075.

https://doi.org/10.1155/2020/6393075

PMid:32215019 PMCid:PMC7079222

Published
2021-12-31
How to Cite
Malekzadeh, S., Edalatmanesh, M. A., Mehrabani, D., & Shariati, M. (2021). Dental Pulp Stem Cells Transplantation Improves Passive Avoidance Memory and Neuroinflammation in Trimethyltin-Induced Alzheimer’s Disease Rat Model. Galen Medical Journal, 10, e2254. https://doi.org/10.31661/gmj.v10i0.2254