Brain-derived neurotrophic factor (BDNF) and microRNAs (miRNAs) play a significant role in the pathogenesis of acute ischemic stroke (AIS). The present study investigates the elevated expression of BDNF and miR-124 in AIS patients. In the present study, serum samples from AIS patients and healthy controls were collected to determine the regulatory role and mechanism of operation of BDNF and to determine the regulatory miRNAs involved in AIS. Using bioinformatics analysis, we identified putative and regulatory miR-124. The effect of miR-124 on BDNF expression was examined in human neuronal cell lines. Moreover, the function of miR-124 in regulating BDNF was analyzed by assessing the serum level of BDNF in both AIS patients and healthy controls. The results indicate that the BDNF level of AIS patients is very low compared with that of controls. In contrast, real-time polymerase chain reaction (RT-PCR) data revealed a very high serum level of miR-124 in AIS patients relative to healthy individuals. The associations of the National Institutes of Health (NIH) stroke scale (NIHSS) score with BDNF and BDNF-related miR-124 serum levels were calculated using Pearson’s/Spearman’s correlation coefficient. The findings revealed a negative correlation between NIHSS score and BDNF level, whereas a positive correlation was observed between NIHSS score and miR-124. In addition, the relationship between serum BDNF and miR-124 was negative in AIS patients. In conclusion, this study provides strong evidence that serum BDNF and the BDNF-regulatory miR-124 may serve as molecular markers for AIS.
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The authors acknowledge the Institution, Institutional Review Board and Ethics Committee for providing support and funding to carrying out this research.
XPW is the corresponding of the manuscript, who planned and designed the experiments for the project. In addition, first draft of the manuscript was written by corresponding author along with JD Research work was carried out and executed equally by JW and QH In addition, part of the research experiments such as statistical analysis was carried out by JD.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
Human and animal rights
This article includes human study and it was approved by the Institutional Ethical Review Board, Ethical Committee, and Research Advisory Committees of the affiliated hospital and research institute. Also, proper written consent was acquired from both the patients and the spectators before collecting samples.
Ambros V (2004) The functions of animal microRNAs Nature 431: 350–355. Proc Natl Acad Sci USA 103:3687–3692Google Scholar
Anacker C, Zunszain PA, Carvalho LA, Pariante CM (2011) The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology 36:415–425CrossRefGoogle Scholar
Arumugam TV, Granger DN, Mattson MP (2005) Stroke and T-cells. Neuromolecular Med 7:229–242CrossRefGoogle Scholar
Bathina S, Srinivas N, Das UN (2016) BDNF protects pancreatic β cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro. Metabolism 65:667–684CrossRefGoogle Scholar
Bathina S, Srinivas N, Das UN (2017) Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats. Biochem Biophys Res Commun 486:406–413CrossRefGoogle Scholar
Bonita R, Mendis S, Truelsen T, Bogousslavsky J, Toole J, Yatsu F (2004) The global stroke initiative. Lancet Neurol 3:391–393CrossRefGoogle Scholar
Mattson M, Duan W, Pedersen W, Culmsee C (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6:69–81CrossRefGoogle Scholar
Meng WD, Sun SJ, Yang J, Chu RX, Tu W, Liu Q (2017) Elevated serum brain-derived neurotrophic factor (BDNF) but not BDNF gene Val66Met polymorphism is associated with autism spectrum disorders. Mol Neurobiol 54:1167–1172CrossRefGoogle Scholar
Muir KW, Tyrrell P, Sattar N, Warburton E (2007) Inflammation and ischaemic stroke. Curr Opin Neurol 20:334–342CrossRefGoogle Scholar
Peng G, Yuan Y, Wu S, He F, Hu Y, Luo B (2015) MicroRNA let-7e is a potential circulating biomarker of acute stage ischemic stroke. Transl Stroke Res 6:437–445CrossRefGoogle Scholar
Smirnova L, Gräfe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21:1469–1477CrossRefGoogle Scholar
Tu WJ, Dong X, Zhao SJ, Yang DG, Chen H (2013) Prognostic value of plasma neuroendocrine biomarkers in patients with acute ischaemic stroke. J Neuroendocrinol 25:771–778CrossRefGoogle Scholar
Tuttolomondo A, Di Raimondo D, di Sciacca R, Pinto A, Licata G (2008) Inflammatory cytokines in acute ischemic stroke. Curr Pharm Des 14:3574–3589CrossRefGoogle Scholar
Vila N, Castillo J, Davalos A, Esteve A, Planas AM, Chamorro A (2003) Levels of anti-inflammatory cytokines and neurological worsening in acute ischemic stroke. Stroke 34:671–675CrossRefGoogle Scholar
Wang J, Gao L, Yang YL (2017) Low serum levels of brain-derived neurotrophic factor were associated with poor short-term functional outcome and mortality in acute ischemic stroke. Mol Neurobiol 54:7335–7342CrossRefGoogle Scholar
Witwer KW, Sisk JM, Gama L, Clements JE (2010) MicroRNA regulation of IFN-β protein expression: rapid and sensitive modulation of the innate immune response. J Immunol 184:2369–2376CrossRefGoogle Scholar
Yasutake C, Kuroda K, Yanagawa T, Okamura T, Yoneda H (2006) Serum BDNF, TNF-α and IL-1β levels in dementia patients. Eur Arch Psychiatry Clin Neurosci 256:402–406CrossRefGoogle Scholar