Abstract
Decreased level of neurotrophic factor brain-derived neurotrophic factor (BDNF) has been supposed to participate in the pathoetiology of Parkinson’s disease (PD). However, the underlying mechanisms of its dysregulation and the functional network between this factor and other transcripts have not been elucidated. In the current study, we measured expressions of BDNF, and four related long non-coding RNAs, namely BDNF-AS, MIR137HG, MIAT and PNKY in blood of PD patients and normal controls to find their expression levels in these patients and propose a possible mechanism for dysregulation of BDNF in PD patients. Notably, we detected down-regulation of all transcripts in the circulation of PD patients compared with controls. There was no significant difference in expression of either gene between male and female PD patients or patients receiving L-Dopa versus those receiving other drugs. Expression of none of genes was correlated with age, disease duration, disease stage, MMSE or UPDRS. Dynamic principal component analysis showed that expression levels of these genes almost clearly separated samples collected from healthy controls and PD patients into their respective groups. This suggests that the observed lncRNAs differences are associated with the pathophysiology of PD, and these lncRNAs might constitute an important biomarker signature for PD.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Andersen RE, Hong SJ, Lim JJ, Cui M, Harpur BA, Hwang E, Delgado RN, Ramos AD, Liu SJ, Blencowe BJ, Lim DA (2019) The long noncoding RNA Pnky is a trans-acting regulator of cortical development in vivo. Dev Cell 49:632–642 e7
Arevalo-Rodriguez I, Smailagic N, Roqué I, Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A, Pedraza OL, Bonfill Cosp X, Cullum S (2015) Mini-mental state examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). The Cochrane database of systematic reviews 2015:CD010783–CD010783
Badrlou E, Ghafouri-Fard S, Omrani MD, Neishabouri SM, Arsang-Jang S, Taheri M, Pouresmaeili F (2021) Expression of BDNF-associated lncRNAs in treatment-resistant schizophrenia patients. J Mol Neurosci 1–11
Chu H-Y (2020) Synaptic and cellular plasticity in Parkinson’s disease. Acta Pharmacol Sin 41:447–452
Ebersbach G, Baas H, Csoti I, Müngersdorf M, Deuschl G (2006) Scales in Parkinson’s disease. J Neurol 253:iv32–iv35
Howells D, Porritt MJ, Wong J, Batchelor P, Kalnins R, Hughes A, Donnan G (2000) Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. Exp Neurol 166:127–135
Huang Y, Yun W, Zhang M, Luo W, Zhou X (2018) Serum concentration and clinical significance of brain-derived neurotrophic factor in patients with Parkinson’s disease or essential tremor. J Int Med Res 46:1477–1485
Jin W (2020) Regulation of BDNF-TrkB signaling and potential therapeutic strategies for Parkinson's disease. J Clin Med 9:257
Klein RL, Lewis MH, Muzyczka N, Meyer EM (1999) Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer. Brain Res 847:314–320
Li E-Y, Zhao P-J, Jian J, Yin B-Q, Sun Z-Y, Xu C-X, Tang Y-C, Wu H (2019) LncRNA MIAT overexpression reduced neuron apoptosis in a neonatal rat model of hypoxic-ischemic injury through miR-211/GDNF. Cell Cycle (Georgetown, Tex) 18:156–166
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408
Modarresi F, Faghihi MA, Lopez-Toledano MA, Fatemi RP, Magistri M, Brothers SP, van der Brug MP, Wahlestedt C (2012) Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol 30:453–459
Palasz E, Wysocka A, Gasiorowska A, Chalimoniuk M, Niewiadomski W, Niewiadomska G (2020) BDNF as a promising therapeutic agent in Parkinson's disease. Int J Mol Sci 21:1170
Poewe W (2012) Global scales to stage disability in PD: the Hoehn and Yahr scale. Rating Scales Parkinsons Dis 115–122
Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G (2015) MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 30:1591–1601
Rezaei O, Nateghinia S, Estiar MA, Taheri M, Ghafouri-Fard S (2021) Assessment of the role of non-coding RNAs in the pathophysiology of Parkinson's disease. Eur J Pharmacol 896:173914
Sun M, Kong L, Wang X, Lu X-G, Gao Q, Geller AI (2005) Comparison of the capability of GDNF, BDNF, or both, to protect nigrostriatal neurons in a rat model of Parkinson's disease. Brain Res 1052:119–129
Thomas KT, Gross C, Bassell GJ (2018) microRNAs sculpt neuronal communication in a tight balance that is lost in neurological disease. Front Mol Neurosci 11:455–455
Tsukahara T, Takeda M, Shimohama S, Ohara O, Hashimoto N (1995) Effects of brain-derived neurotrophic factor on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys. Neurosurgery 37: 733–739; discussion 739–41
Wang Y, Liu H, Zhang B-S, Soares JC, Zhang XY (2016) Low BDNF is associated with cognitive impairments in patients with Parkinson’s disease. Parkinsonism Relat Disord 29:66–71
Zhang Y, Yan L, Cao Y, Kong G, Lin C (2016) Long noncoding RNA BDNF-AS protects local anesthetic induced neurotoxicity in dorsal root ganglion neurons. Biomed Pharmacother 80:207–212
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This study was financially supported by Grant number 29300 from Medical School of Shahid Beheshti University of Medical Sciences.
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SGF wrote the manuscript and revised it. AS supervised and designed the study. SJ, BMH and HHJ performed the experiment. SE analyzed the data. MD was the clinical consultant and assessed patients for inclusion in the study. All authors read and approved the submitted version.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent forms were obtained from all study participants. The study protocol was approved by the ethical committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1400.568). All methods were performed in accordance with the relevant guidelines and regulations.
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Akbari, M., Gholipour, M., Hussen, B.M. et al. Expression of BDNF-Associated lncRNAs in Parkinson’s disease. Metab Brain Dis 37, 901–909 (2022). https://doi.org/10.1007/s11011-022-00946-1
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DOI: https://doi.org/10.1007/s11011-022-00946-1