How MicroRNA contributes to Neuroscience?

Nervous system, Neuroscience and MicroRNA

Nervous system and Neuroscience

The nervous system is a highly complex system that coordinates physical behavior and perception by sending signals around the body. The nervous system is closely related to the sensory organs to respond to changes in the external environment and cooperates with the endocrine system to endow the organism with the ability to adapt to the environment[1]. Defined at the cellular level, the nervous system consists primarily of neurons (nerve cells), in addition to glial cells that provide structural and metabolic support[2]. Defined at the system level, the nervous system consists of the central nervous system (CNS) and the peripheral nervous system (PNS). CNS consists primarily of the brain and spinal cord, the main function is to integrate information and send signals to the body to control coordination[3]. PNS consists of the nerves and ganglia outside the brain and spinal cord, the main function is to perceive and coordinate the reception and transmission of information[4, 5].

 

Figure.1a. Human nervous system. b. Structure of a typical neuron

 

Neuroscience is a multidisciplinary scientific study of the nervous system[6]. The disciplines it covers include physiology, anatomy, molecular biology, developmental biology, cytology, physics, mathematical modeling, etc.[7]. Neuroscience has made enormous contributions to the study of biological learning, memory, behavior, consciousness, and perception[8]. With the rise of molecular biology and electrophysiology, neuroscience was regarded as an independent discipline in the middle and late 20th century and gradually developed into the stage of modern neuroscience[9]. Since then, neuroscience has been widely developed and derived many branches, and even extended to the field of computers and chips.

 

MicroRNA

MicroRNAs (miRNA) refers to a kind of short (about 22 nucleotides) single-stranded non-coding RNA[10]. There are more than 500 human miRNAs that have been manually sorted and confirmed[11]. The first miRNA was identified in the 1990s, and after it was discovered that it is an important regulator of physiological and pathological processes, it has quickly become a research hotspot, and the number of related publications has reached a peak in recent years[12, 13]. MiRNAs can silence the expression of target genes by complementary binding to mRNAs, thereby performing their functions as regulators[14]. And miRNAs are deeply involved in the pathological process of many types of diseases, including cancer, heart disease, nerve system diseases, kidney diseases, obesity, etc.[15].

Molecular mechanism, research methods of miRNA and its connection with neuroscience

Molecular mechanism and Research methods

The mature form of miRNAs is formed by the cleavage of its precursor (pre-miRNA) by the Dicer enzyme. Pre-miRNAs are single-stranded RNAs transcribed from templates and self-complementary to form hairpin structures, and after Dicer enzyme cleavage, the hairpin structure’s 5′ and 3′ ends will become miRNA-5p (miR-5p) and miRNA-3p (miR-3p). Normally miR-3p is useless and degrades rapidly, a few miR-3p become miRNAs with important physiological functions[16].

 

MiRNA-related research is similar to the research strategy of other metabolic factors and signaling factors, common research tools include miRNA mimics, inhibitors, agomir and antagomir. MiRNA mimics can mimic the physiological functions of mature miRNAs, are usually used in in vitro cell experiments, and need to be transfected into cells[17]. MiRNA agomirs are chemically modified mimics. Compared with ordinary mimics, agomirs have a stronger ability to pass through the membrane and are not easy to degrade, usually used in in vivo experiments based on animal models. And agomir can achieve non-transfected cell treatment, so it can also be used for cell lines that are not suitable for transfection.[18]

 

MiRNA in neuroscience

MiRNAs are numerous and diverse in type and function, and their functions are involved in various physiological and pathological processes, of which the regulation of the nervous system is an important part. MiRNAs play roles in social and anxiety-related behavior, and participate in the pathological process of a variety of nervous system-related diseases, including Parkinson’s disease (PD)[19], Alzheimer’s disease (AD)[20], spectrum disorders (ASD), anxiety disorders[21], etc.

 

Su et al. find that miR-26a plays a role in Parkinson’s pathology[22]. They screened out the involvement of miR-26a in Death-associated protein kinase 1 (DAPK1)-induced synucleinopathy and dopaminergic neuron degeneration in PD by analyzing Clinical samples from PD patients, PD mice, and in vitro cell models. The data showed that activation of DAPK1 was often accompanied by a decrease in miR-26a. And then, they use miR-26a antagomir to treat WT mice to try to identify the role of miR-26a in DAPK1-induced PD-like pathological and behavioral changes. They eventually found that the inhibition of miR-26a and the activation of DAPK1 can both induce PD-like pathological and behavioral changes, finally confirming that DAPK1/miR-26a signaling is an important link in Parkinson’s disease.

 

In a publication on AD, Chen et al. found and verified the role of miR-331-3p and miR-9-5p in the pathology of AD[23]. First, they identified miR-331-3p and miR-9-5p as possible associations with autophagy in AD by screening RNA-seq miRNA expression profiling data. And then, they found that these two miRNAs are down-regulated in early-stage of AD mice and up-regulated in late-stage of AD mice. After that, they use miR-331-3p and miR-9-5p antagomir treats the late-stage AD mice model and found that the behavior and cognitive ability of the mice were improved. Besides, they identified these two miRNAs can target autophagy-related genes. Taken together, they finally concluded that inhibition of miR-331-3p and miR-9-5p could improve AD by enhancing autophagy.

 

Conclusion

Neuroscience research is of great significance for solving difficult diseases related to the nervous system. As important physiological and pathological regulators, miRNAs become potential targets for a variety of diseases due to their large number and diverse functions. Therefore, the research on the role of miRNA in the regulation of the nervous system is of great value.

 

Where to get MicroRNA products and services?

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It is our pleasure to help relative researches to move forward. All the products of AcceGen are strictly comply with international standards. For more detailed information, please visit our product portfolio or contact inquiry@accegen.com.

 

References

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5. Slide show: How your brain works – Mayo Clinic.mayocliniccom 2016.

6. Neuroscience.Merriam-Webster Medical Dictionary.

7. Kandel ER: Overall perspective.In Principles of Neural Science, Fifth Edition.McGraw-Hill Education; 2012

8. Kandel ER: The last frontier of the biological sciences – their ultimate challenge – is to understand the biological basis of consciousness and the mental processes by which we perceive, act, learn, and remember.In Principles of Neural Science, Fifth Edition.McGraw-Hill Education; 2012

9. Cowan WM, Harter DH, Kandel ER: The emergence of modern neuroscience: some implications for neurology and psychiatry.Annu Rev Neurosci 2000, 23:343-391.

10. Qureshi A, Thakur N, Monga I, Thakur A, Kumar M: VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets.Database (Oxford) 2014, 2014.

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12. Lee RC, Feinbaum RL, Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.Cell 1993, 75:843-854.

13. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G: The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.Nature 2000, 403:901-906.

14. Bartel DP: MicroRNAs: target recognition and regulatory functions.Cell 2009, 136:215-233.

15. Fromm B, Billipp T, Peck LE, Johansen M, Tarver JE, King BL, Newcomb JM, Sempere LF, Flatmark K, Hovig E, Peterson KJ: A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome.Annu Rev Genet 2015, 49:213-242.

16. Feng Q, Zhang H, Nie X, Li Y, Chen WD, Wang YD: miR-149* Suppresses Liver Cancer Progression by Down-Regulating Tumor Necrosis Factor Receptor 1-Associated Death Domain Protein Expression.Am J Pathol 2020, 190:469-483.

17. Lu TX, Rothenberg ME: MicroRNA.J Allergy Clin Immunol 2018, 141:1202-1207.

18. abm: https://www.abmgood.com/Synthetic-miRNA-Mimics-and-Agomirs.html.

19. Goh SY, Chao YX, Dheen ST, Tan EK, Tay SS: Role of MicroRNAs in Parkinson’s Disease.Int J Mol Sci 2019, 20.

20. Nunomura A, Perry G: RNA and Oxidative Stress in Alzheimer’s Disease: Focus on microRNAs.Oxid Med Cell Longev 2020, 2020:2638130.

21. Narayanan R, Schratt G: miRNA regulation of social and anxiety-related behaviour.Cell Mol Life Sci 2020, 77:4347-4364.

22. Su Y, Deng MF, Xiong W, Xie AJ, Guo J, Liang ZH, Hu B, Chen JG, Zhu X, Man HY, et al: MicroRNA-26a/Death-Associated Protein Kinase 1 Signaling Induces Synucleinopathy and Dopaminergic Neuron Degeneration in Parkinson’s Disease.Biol Psychiatry 2019, 85:769-781.

23. Chen ML, Hong CG, Yue T, Li HM, Duan R, Hu WB, Cao J, Wang ZX, Chen CY, Hu XK, et al: Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer’s disease by enhancing autophagy.Theranostics 2021, 11:2395-2409.