Translational neuroscience

Translational neuroscience is the field of study which applies neuroscience research to translate or develop into clinical applications and novel therapies for nervous system disorders.^[1][2] The field encompasses areas such as deep brain stimulation, brain machine interfaces, neurorehabilitation and the development of devices for the sensory nervous system such as the use of auditory implants, retinal implants, and electronic skins.

Classification

Translational neuroscience research is categorized into stages of research, which are classified using a five tier system (T0-T4), beginning with basic science research and ending with the public health applications of basic scientific discoveries.^[3] While once considered a linear progression from basic science to public health application, translational research, and translational neuroscience in particular, is now regarded as a cyclic, where public health needs inform basic science research, which then works to discover the mechanisms of public health issues and works towards clinical and public health implementation.

The stages of translational neuroscience research are as follows:^[4]

• T0: Basic science research
• T1: Preclinical research
• T2: Clinical research or Clinical neuroscience
• T3: Clinical implementation
• T4: Public health

Methods

Electrophysiology

Electrophysiology is used within translational neuroscience as a means of studying the electric properties of neurons in animal models as well as to investigate the properties of human neurological dysfunction.^[3] Techniques used in animal models, such as patch-clamp recordings, have been used to investigate how neurons respond to pharmacological agents. Electroencephalography (EEG) and magnetoencephalography (MEG) are both used to measure electrical activity in the human brain, and can be used in clinical settings to localize the source of neurological dysfunction in conditions such as epilepsy, and can also be used in a research setting to investigate the differences in electrical activity in the brain between normal and neurologically dysfunctional individuals.^[3]

Neuroimaging

An fMRI scanner.

Neuroimaging comprises a variety of techniques used to observe the activity or the structures of, or within, the nervous system. Positron emission tomography (PET) has been used in animal models, such as non-human primate and rodent, to identify and target molecular mechanisms of neurological disease, and to study the neurological impact of pharmacological drug addiction.^[5][6][7] Similarly, functional magnetic resonance imaging (fMRI) has been used to investigate the neurological mechanisms of pharmacological drug addiction, the neurological mechanisms of mood and anxiety disorders in elderly populations, and the neurological mechanisms of disorders such as schizophrenia.^{[8][9][10][11]}

Gene therapy

Gene therapy is the delivery of nucleic acid as a treatment for a disorder. In translational neuroscience, gene therapy is the delivery of nucleic acid as a treatment for a neurological disorder. Gene therapy has been proven effective at treating a variety of disorders, including neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD), in rodent and non-human primate models, and in humans, via the application of neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF), and via the application of enzymes such as glutamic acid decarboxylase (GAD), which commonly use adeno-associated viruses (AAV) as a vector.^{[12][13][14][15]}

Stem cells

Stem cells, particularly induced pluripotent stem cells (iPSCs), are utilized in translational neuroscience research as not only a treatment for nervous system disorders, but also as the source for models of neural dysfunction.^[16] For example, due to the central nervous system's limited regenerative abilities, human embryonic stem cells (hESCs), a type of pluripotent stem cell, has been used as a replacement for damaged neurons, a novel approach that involves the surgical transplantation of fetal stem cells^[17]

Applications

Neurodevelopmental disorders

Neurodevelopmental disorders are characterized as disorders where the development of the nervous system was disrupted, and encompasses disorders such as learning disabilities, autism spectrum disorders (ASD), epilepsy, and certain neuromuscular disorders. Translational neuroscience research involves efforts to uncover the molecular mechanisms for these disorders and work towards cures in patient populations.^[16][18][19] Additionally, translational neuroscience research has focused on elucidating the cause of neurodevelopmental disorders, whether it be genetic, environmental, or a combination of both, as well as tactics for prevention, if possible.^[19]

Neurodegenerative disorders

Neurodegenerative disorders are a result of neuronal loss of function over time which lead to cell death. Examples of neurodegenerative disorders include Alzheimer's disease, Parkinson's disease, and Huntington's disease.^[20] The focus of translational neuroscience research is to investigate the molecular mechanisms for these disorders, and to investigate the mechanisms of drug delivery to treat these disorders, including an investigation into the impact of the blood-brain barrier on drug delivery, and the role of the body's immune system in neurodegenerative disorders.^[16]

See also

• Translational medicine
• Knowledge transfer

References

1. Translational Neuroscience, University of Chicago
2. Translational NeuroscienceDe Gruyter
3. Tuszynski MH (2012). "Introduction". Translational Neuroscience. Garcia-Rill, Edgar. Chichester, West Sussex, UK: Wiley-Blackwell. pp. 1–6. doi:10.1007/978-1-4899-7654-3_1. ISBN 9781118260470. OCLC 769189209.
4. "Translational Science Spectrum". National Center for Advancing Translational Sciences. 2015-03-12. Retrieved 2019-02-25.
5. Higuchi M, Maeda J, Ji B, Tokunaga M, Zhang MR, Maruyama M, Ono M, Fukumura T, Suhara T (2012). "PET applications in animal models of neurodegenerative and neuroinflammatory disorders". In Carter CS, Dalley JW (eds.). Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences. Vol. 11. Springer Berlin Heidelberg. pp. 45–64. doi:10.1007/7854_2011_167. ISBN 9783642287114. PMID 22016108.
6. Gould RW, Porrino LJ, Nader MA (2012). "Nonhuman primate models of addiction and PET imaging: dopamine system dysregulation". In Carter CS, Dalley JW (eds.). Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences. Vol. 11. Springer Berlin Heidelberg. pp. 25–44. doi:10.1007/7854_2011_168. ISBN 9783642287114. PMC 3831150. PMID 22020537.
7. Aarons AR, Talan A, Schiffer WK (2012). "Experimental protocols for behavioral imaging: seeing animal models of drug abuse in a new light". In Carter CS, Dalley JW (eds.). Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences. Vol. 11. Springer Berlin Heidelberg. pp. 93–115. doi:10.1007/7854_2012_206. ISBN 9783642287114. PMID 22411423.
8. Libby LA, Ragland JD (2012). "FMRI as a measure of cognition related brain circuitry in schizophrenia". In Carter CS, Dalley JW (eds.). Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences. Vol. 11. Springer Berlin Heidelberg. pp. 253–67. doi:10.1007/7854_2011_173. ISBN 9783642287114. PMC 4332581. PMID 22105156.
9. Salo R, Fassbender C (2012). "Structural, functional and spectroscopic MRI studies of methamphetamine addiction". In Carter CS, Dalley JW (eds.). Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences. Vol. 11. Springer Berlin Heidelberg. pp. 321–64. doi:10.1007/7854_2011_172. ISBN 9783642287114. PMID 22094881.
10. Minzenberg MJ (2012). "Pharmacological MRI approaches to understanding mechanisms of drug action". In Carter CS, Dalley JW (eds.). Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences. Vol. 11. Springer Berlin Heidelberg. pp. 365–88. doi:10.1007/7854_2011_177. ISBN 9783642287114. PMID 22057623.
11. Andreescu C, Aizenstein H (2012). "MRI studies in late-life mood disorders". In Carter CS, Dalley JW (eds.). Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences. Vol. 11. Springer Berlin Heidelberg. pp. 269–87. doi:10.1007/7854_2011_175. ISBN 9783642287114. PMC 3733498. PMID 22167336.
12. Kaplitt MG, During MJ (2016). "GAD Gene Therapy for Parkinson's Disease". In Tuszynski MH (ed.). Translational Neuroscience. Springer US. pp. 89–98. doi:10.1007/978-1-4899-7654-3_5. ISBN 9781489976543. {{cite book}}: |work= ignored (help)
13. Bankiewicz K, Sebastian WS, Samaranch L, Forsayeth J (2016). "GDNF and AADC Gene Therapy for Parkinson's Disease". In Tuszynski MH (ed.). Translational Neuroscience. Springer US. pp. 65–88. doi:10.1007/978-1-4899-7654-3_4. ISBN 9781489976543. {{cite book}}: |journal= ignored (help)
14. Tuszynski MH, Nagahara AH (2016). "NGF and BDNF Gene Therapy for Alzheimer's Disease". In Tuszynski MH (ed.). Translational Neuroscience. Springer US. pp. 33–64. doi:10.1007/978-1-4899-7654-3_3. ISBN 9781489976543. {{cite book}}: |journal= ignored (help)
15. Murlidharan G, Samulski RJ, Asokan A (2016). "Gene Therapy of CNS Disorders Using Recombinant AAV Vectors". In Tuszynski MH (ed.). Translational Neuroscience. Springer US. pp. 9–32. doi:10.1007/978-1-4899-7654-3_2. ISBN 9781489976543. {{cite book}}: |journal= ignored (help)
16. Nikolich K, Hyman SE (2016). "What Do We Know about Early Onset Neurodevelopmental Disorders?". Translational neuroscience : toward new therapies. Cambridge, MA: MIT Press. ISBN 9780262329859. OCLC 919201534.
17. Bongso A, Lee EH (2011). "From Stem Cells to Neurons: Translating Basic Science into Preclinical Animal Validation". Stem cells : from bench to bedside (2nd ed.). Singapore: World Scientific. ISBN 9789814289399. OCLC 738438261.
18. Owen MJ (2015). "Psychotic Disorders and the Neurodevelopmental Continuum". Translational Neuroscience: Toward New Therapies. Nikolich, Karoly, Hyman, Steven E. The MIT Press. ISBN 9780262329859.
19. Heckers S, Hyman SE, Bourgeron T, Cuthbert BN, Gur RE, Joyce C, Meyer-Lindenberg A, Owen MJ, State MW (2015). "Neurodevelopmental Disorders: What Is to Be Done?". Translational Neuroscience: Toward New Therapies. Nikolich, Karoly, Hyman, Steven E. The MIT Press. ISBN 9780262329859.
20. "Neurodegenerative Diseases". National Institute of Environmental Health Sciences. Retrieved 2019-02-27.