Timokinon, sağlıklı sıçanlarda hipokampal miR-26b, miR-124 ve miR-29a mikroRNA'larının ekspresyonlarını etkiler
Year 2024,
, 353 - 358, 27.10.2024
Ayça Doğan Mollaoğlu
,
Merve Beker
,
Tuğçe Dallı
Birsen Elibol
Abstract
Amaç: Nigella sativa'nın ana biyoaktif bileşeni olan Thymoquinone (TQ), kan beyin bariyerini geçerek nöroprotektif ve nöromodülatör aktiviteler gösterir. Bu çalışmanın amacı, TQ uygulamasının sağlıklı sıçanların hipokampüsünde 26b, 124, 29a ve 29c mikroRNA'larının (miR) ekspresyonları üzerindeki etkisini araştırmaktır.
Yöntem: TQ (20 mg kg-1 d-1) yetişkin sıçanlara 15 gün boyunca intragastrik olarak uygulanmıştır. İlgili genlerin mikroRNA seviyeleri gerçek zamanlı polimeraz zincir reaksiyonu kullanılarak analiz edilmiştir.
Bulgular: TQ uygulaması miR-26b ve miR-124'ün ifade profillerini önemli ölçüde aşağı düzenlerken miR-29a'nın ifadesini yukarı düzenlemiştir. miR-29c'nin ifade düzeyinde anlamlı bir etki gözlenmemiştir.
Sonuç: TQ, beyinde yüksek oranda ifade edilen miR-26b, miR-124 ve miR-29a'nın ifadelerini değiştirerek sağlıklı beyin ve/veya merkezi sinir sistemi fonksiyonlarında faydalı bir role sahip olabilir.
Ethical Statement
The experimental protocol of this study was approved by the Committee for Animal Research Ethics in Bezmialem Vakif University (2015/229).
Supporting Institution
Bezmialem Vakif University
Project Number
BVU-BAP(12.2014/2)
Thanks
This study was supported by the grant from Bezmialem Vakif University Scientific Research Found (BVU-BAP) (12.2014/2).
References
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- Jiao S, Liu Y, Yao Y, Teng J. miR-124 promotes proliferation and neural differentiation of neural stem cells through targeting DACT1 and activating Wnt/beta-catenin pathways. Mol Cell Biochem. 2018;449(1-2):305–314. doi: 10.1007/s11010-018-3367-z
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- He C, Wang Q, Fan D, et al. MicroRNA-124 influenced depressive symptoms via large-scale brain connectivity in major depressive disorder patients. Asian J Psychiatr. 2024;95:104025. doi:10.1016/j.ajp.2024.104025
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- Rusu-Nastase EG, Lupan AM, Marinescu CI, Neculachi CA, Preda MB, Burlacu A. MiR-29a Increase in Aging May Function as a Compensatory Mechanism Against Cardiac Fibrosis Through SERPINH1 Downregulation. Front Cardiovasc Med. 2022;8:810241. doi:10.3389/fcvm.2021. 810241
- Ma R, Wang M, Gao S, et al. miR-29a Promotes the Neurite Outgrowth of Rat Neural Stem Cells by Targeting Extracellular Matrix to Repair Brain Injury. Stem Cells Dev. 2020;29(9):599-614. doi:10.1089/scd.2019.0174
- Alhebshi, A H, Gotoh M, Suzuki I. Thymoquinone protects cultured rat primary neurons against amyloid beta-induced neurotoxicity. Biochem Biophys Res Commun. 2013;433: 362–367. doi: 10.1016/j.bbrc. 2012.11.139
- Bin Sayeed MS, Shams T, Fahim Hossain S, et al. Nigella sativa L. seeds modulate mood, anxiety and cognition in healthy adolescent males. J Ethnopharmacol. 2014;152(1):156-162. doi:10.1016/j.jep.2013.12.050
Year 2024,
, 353 - 358, 27.10.2024
Ayça Doğan Mollaoğlu
,
Merve Beker
,
Tuğçe Dallı
Birsen Elibol
Project Number
BVU-BAP(12.2014/2)
References
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- Brennan, G.P., Henshall, D.C. MicroRNAs as regulators of brain function and targets for treatment of epilepsy. Nat Rev Neurol. 2020;16, 506–519. doi.org/10.1038/s41582-020-0369-8
- Smirnova L, Gräfe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG. Regulation of miRNA expression during neural cell specification. Eur J Neurosci. 2005;21(6):1469-1477. doi:10.1111/j.1460-9568.2005.03978.x
- Xu S, Zhang R, Niu J, et al. Oxidative stress mediated-alterations of the microRNA expression profile in mouse hippocampal neurons. Int J Mol Sci. 2012;13(12):16945–16960. doi.org/10.3390 /ijms1 31216945
- Burdock GA. Assessment of black cumin (Nigella sativa L.) as a food ingredient and putative therapeutic agent. Regul Toxicol Pharmacol. 2022;128:105088. doi:10.1016/j.yrtph. 2021.105088
- Tiruppur Venkatachallam SK, Pattekhan H, Divakar S, Kadimi US. Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxide. J Food Sci Technol. 2010;47(6):598-605. doi:10.1007/s13197-010-0109-y
- Ahmad A, Husain A, Mujeeb M, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013;3(5):337-352. doi:10.1016/S2221-1691(13) 60075-1
- Jakaria M, Cho DY, Ezazul Haque M, et al. Neuropharmaco-logical Potential and Delivery Prospects of Thymoquinone for Neurological Disorders. Oxid Med Cell Longev. 2018;2018: 1209801. doi:10.1155/2018/ 1209801
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- Ardah MT, Merghani MM, Haque ME. Thymoquinone prevents neurodegeneration against MPTP in vivo and modulates α-synuclein aggregation in vitro. Neurochem Int. 2019;128:115-126. doi:10.1016/j.neuint.2019.04.014
- Cascella M, Bimonte S, Barbieri A, et al. Dissecting the Potential Roles of Nigella sativa and Its Constituent Thymoquinone on the Prevention and on the Progression of Alzheimer's Disease. Front Aging Neurosci. 2018;10:16. doi:10.3389/fnagi.2018.00016
- Sayeed MSB, Asaduzzaman M, Morshed H, Hossain MM, Kadir MF, Rahman MR. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. J Ethnopharmacol. 2013;148;(3):780–786. doi.org/10.1016/j.jep.2013.05.004.
- Das SS., Kannan R, George S, et al. Thymoquinone-rich black cumin oil improves sleep quality, alleviates anxiety/stress on healthy subjects with sleep disturbances—A pilot polysomnography study. J Herb Med. 2022;32:100507. doi.org/10.1016/j.hermed.2021.100507.
- Aquib M, Najmi AK, Akhtar M. Antidepressant Effect of Thymoquinone in Animal Models of Depression. Drug Res (Stuttg). 2015;65(9):490-494. doi:10.1055/s-0034-1389920
- Mokhtari T, Tu Y, Hu L. Involvement of the hippocampus in chronic pain and depression. Brain Science Advances. 2019;5(4):288-298. doi:10.26599/BSA.2019.9050025
- Elibol B, Beker M, Terzioglu-Usak S, Dalli T, Kilic U. Thymoquinone administration ameliorates Alzheimer's disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta1-42 infused rat model. Phytomedicine. 2020;79:153324. doi:10.1016/j.phymed. 2020.153324
- Gao J, Liu QG. The role of miR-26 in tumors and normal tissues (Review). Oncol Lett. 2011;2(6):1019-1023. doi:10.3892/ol.2011.413
- Absalon S, Kochanek DM, Raghavan V, Krichevsky AM. MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tau-phosphorylation, and apoptosis in postmitotic neurons. J Neurosci. 2013;33(37):14645-14659. doi:10.1523 /JNEUROSCI.1327-13.2013
- Dill H, Linder B, Fehr A, Fischer U. Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2. Genes Dev. 2012;26(1):25-30. doi:10.1101/gad. 177774.111
- Caputo V, Sinibaldi L, Fiorentino A, et al. Brain derived neurotrophic factor (BDNF) expression is regulated by microRNAs miR-26a and miR-26b allele-specific binding. PLoS One. 2011;6(12):e28656. doi:10.1371/journal.pone. 0028656
- Arancibia S, Silhol M, Moulière F, et al. Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis. 2008;31(3):316-326. doi:10.1016/j.nbd.2008.05.012
- Gao H, Han Z, Huang S, et al. Intermittent hypoxia caused cognitive dysfunction relate to miRNAs dysregulation in hippocampus. Behav Brain Res. 2017;335: 80–7.
- Chivero ET, Liao K, Niu F, et al. Engineered extracellular vesicles loaded with miR-124 attenuate cocaine-mediated activation of microglia. Front Cell Dev Biol. 2020;8:573.
- Wang, Y., Huang, C., Chintagari, N.R., Xi, D., Weng, T., Liu, L. miR-124 regulates fetal pulmonary epithelial cell maturation. Am J Physiol Lung Cell Mol Physiol. 2015;309: L400–L413.
- Deo M, Yu JY, Chung KH, Tippens M, Turner DL. Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides [published correction appears in Dev Dyn. 2007;236(3):912]. Dev Dyn. 2006;235(9):2538-2548. doi:10.1002/dvdy.20847
- Jiao S, Liu Y, Yao Y, Teng J. miR-124 promotes proliferation and neural differentiation of neural stem cells through targeting DACT1 and activating Wnt/beta-catenin pathways. Mol Cell Biochem. 2018;449(1-2):305–314. doi: 10.1007/s11010-018-3367-z
- Xue Q, Yu C, Wang Y, et al. miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/ GSK3beta pathway by targeting Rap2a. Sci Rep. 2016;6:26781. doi:10.1038/srep 26781
- Higuchi F, Uchida S, Yamagata H, et al. Hippocampal MicroRNA-124 Enhances Chronic Stress Resilience in Mice. J Neurosci. 2016;36(27):7253-7267. doi:10.1523/JNEUROSCI. 0319-16.2016
- Bahi A, Chandrasekar V, Dreyer JL. Selective lentiviral-mediated suppression of microRNA124a in the hippocampus evokes antidepressants-like effects in rats. Psychoneuroendocrinology. 2014;46, 78–87.
- Pan-Vazquez A, Rye N, Ameri M, et al. Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety. Mol Brain. 2015;8:40. doi:10.1186/s13041-015-0128-8
- He C, Wang Q, Fan D, et al. MicroRNA-124 influenced depressive symptoms via large-scale brain connectivity in major depressive disorder patients. Asian J Psychiatr. 2024;95:104025. doi:10.1016/j.ajp.2024.104025
- Fang M, Wang J, Zhang X, et al. The miR-124 regulates the expression of BACE1/β-secretase correlated with cell death in Alzheimer's disease. Toxicol Lett. 2012;209(1):94-105. doi:10.1016/j.toxlet.2011.11.032
- Wang X, Liu D, Huang HZ, et al. A Novel MicroRNA-124/PTPN1 Signal Pathway Mediates Synaptic and Memory Deficits in Alzheimer's Disease. Biol Psychiatry. 2018;83(5):395-405. doi:10.1016/j.biopsych.2017.07.023
- Ho VM, Dallalzadeh LO, Karathanasis N, et al. GluA2 mRNA distribution and regulation by miR-124 in hippocampal neurons. Mol Cell Neurosci. 2014;61:1-12. doi:10.1016/ j.mcn.2014.04.006
- Khan FZ, Mostaid MS, Apu MNH. Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer's disease. Heliyon. 2022;8(7):e09874. doi:10.1016/j.heliyon.2022.e09874
- Bai X, Tang Y, Yu M, et al. Downregulation of blood serum microRNA 29 family in patients with Parkinson's disease. Sci Rep. 2017;7(1):5411. doi:10.1038/s41598-017-03887-3
- Li H, Mao S, Wang H, Zen K, Zhang C, Li L. MicroRNA-29a modulates axon branching by targeting doublecortin in primary neurons. Protein Cell. 2014;5(2):160-169. doi:10. 1007/s13238-014-0022-7
- Lippi G, Steinert JR, Marczylo EL, et al. Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology. J Cell Biol. 2011;194(6):889-904. doi:10. 1083/jcb.201103006
- Papadopoulou AS, Serneels L, Achsel T, et al. Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice. Neurobiol Dis. 2015;73:275-288. doi:10.1016/j.nbd.2014.10.006
- Rusu-Nastase EG, Lupan AM, Marinescu CI, Neculachi CA, Preda MB, Burlacu A. MiR-29a Increase in Aging May Function as a Compensatory Mechanism Against Cardiac Fibrosis Through SERPINH1 Downregulation. Front Cardiovasc Med. 2022;8:810241. doi:10.3389/fcvm.2021. 810241
- Ma R, Wang M, Gao S, et al. miR-29a Promotes the Neurite Outgrowth of Rat Neural Stem Cells by Targeting Extracellular Matrix to Repair Brain Injury. Stem Cells Dev. 2020;29(9):599-614. doi:10.1089/scd.2019.0174
- Alhebshi, A H, Gotoh M, Suzuki I. Thymoquinone protects cultured rat primary neurons against amyloid beta-induced neurotoxicity. Biochem Biophys Res Commun. 2013;433: 362–367. doi: 10.1016/j.bbrc. 2012.11.139
- Bin Sayeed MS, Shams T, Fahim Hossain S, et al. Nigella sativa L. seeds modulate mood, anxiety and cognition in healthy adolescent males. J Ethnopharmacol. 2014;152(1):156-162. doi:10.1016/j.jep.2013.12.050