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.
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]
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 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 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, 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]
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 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]
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.
In philosophy and neuroscience, neuroethics is the study of both the ethics of neuroscience and the neuroscience of ethics. The ethics of neuroscience concerns the ethical, legal and social impact of neuroscience, including the ways in which neurotechnology can be used to predict or alter human behavior and "the implications of our mechanistic understanding of brain function for society... integrating neuroscientific knowledge with ethical and social thought".
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption. Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the brain, energy failure, increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation. Of these mechanisms, neuroprotective treatments often target oxidative stress and excitotoxicity—both of which are highly associated with CNS disorders. Not only can oxidative stress and excitotoxicity trigger neuron cell death but when combined they have synergistic effects that cause even more degradation than on their own. Thus limiting excitotoxicity and oxidative stress is a very important aspect of neuroprotection. Common neuroprotective treatments are glutamate antagonists and antioxidants, which aim to limit excitotoxicity and oxidative stress respectively.
HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during the late stages of the disease, when immunodeficiency is severe. HAND may include neurological disorders of various severity. HIV-associated neurocognitive disorders are associated with a metabolic encephalopathy induced by HIV infection and fueled by immune activation of macrophages and microglia. These cells are actively infected with HIV and secrete neurotoxins of both host and viral origin. The essential features of HIV-associated dementia (HAD) are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss.
Neuroimmunology is a field combining neuroscience, the study of the nervous system, and immunology, the study of the immune system. Neuroimmunologists seek to better understand the interactions of these two complex systems during development, homeostasis, and response to injuries. A long-term goal of this rapidly developing research area is to further develop our understanding of the pathology of certain neurological diseases, some of which have no clear etiology. In doing so, neuroimmunology contributes to development of new pharmacological treatments for several neurological conditions. Many types of interactions involve both the nervous and immune systems including the physiological functioning of the two systems in health and disease, malfunction of either and or both systems that leads to disorders, and the physical, chemical, and environmental stressors that affect the two systems on a daily basis.
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.
National Brain Research Centre is a research institute in Manesar, Gurgaon, India.It is an autonomous institute under the Department of Biotechnology, Ministry of Science and Technology, Government of India. The institute is dedicated to research in neuroscience and brain functions in health and diseases using multidisciplinary approaches. This is the first autonomous institute by DBT to be awarded by the Ministry of Education, Government of India, formerly known as the Ministry of Human Resource Development, in May 2002. NBRC was dedicated to the nation by the Honorable President of India Dr. A.P.J. Abdul Kalam in December 2003. The founder chairman of NBRC Society is Prof. Prakash Narain Tandon, whereas the founder director Prof. Vijayalakshmi Ravindranath was followed by Prof. Subrata Sinha and Prof. Neeraj Jain. The current director of NBRC is Prof. Krishanu Ray.
Neurogenetics studies the role of genetics in the development and function of the nervous system. It considers neural characteristics as phenotypes, and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same species, may not be identical. As the name implies, it draws aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code an organism carries affects its expressed traits. Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.
Nervous system diseases, also known as nervous system or neurological disorders, refers to a small class of medical conditions affecting the nervous system. This category encompasses over 600 different conditions, including genetic disorders, infections, cancer, seizure disorders, conditions with a cardiovascular origin, congenital and developmental disorders, and degenerative disorders.
Anne Buckingham Young is an American physician and neuroscientist who has made major contributions to the study of neurodegenerative diseases, with a focus on movement disorders like Huntington's disease and Parkinson's disease. Young completed her undergraduate studies at Vassar College and earned a dual MD/PhD from Johns Hopkins Medical School. She has held faculty positions at University of Michigan and Harvard University. She became the first female chief of service at Massachusetts General Hospital when she was appointed Chief of Neurology in 1991. She retired from this role and from clinical service in 2012. She is a member of many academic societies and has won numerous awards. Young is also the only person to have been president of both the international Society for Neuroscience and the American Neurological Association.
Clinical neuroscience is a branch of neuroscience that focuses on the scientific study of fundamental mechanisms that underlie diseases and disorders of the brain and central nervous system. It seeks to develop new ways of conceptualizing and diagnosing such disorders and ultimately of developing novel treatments.
Maria Luisa Escolar is a pediatrician, clinical professor, and researcher who specializes in pediatric neurodevelopmental disabilities. She is Founder and Director of the Program for the Study of Neurodevelopment in Rare Disorders at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center. Escolar is nationally and internationally known for her research and clinical care of children with leukodystrophies, lysosomal storage diseases, and other inherited metabolic diseases.
Rajiv Ratan is an Indian American academic, professor, administrator and scientist based in New York. He is the Burke Professor of Neurology and Neuroscience at Weill Cornell Medicine. Since 2003, he has served as the executive director of Burke Neurological Institute and as a member of the Council of Affiliated Deans of Weill Cornell Medicine.
The neuroscience of aging is the study of the changes in the nervous system that occur with ageing. Aging is associated with many changes in the central nervous system, such as mild atrophy of the cortex that is considered non-pathological. Aging is also associated with many neurological and neurodegenerative disease such as amyotrophic lateral sclerosis, dementia, mild cognitive impairment, Parkinson's disease, and Creutzfeldt–Jakob disease.
Non-invasive cerebellar stimulation is the application of non-invasive neurostimulation techniques on the cerebellum to modify its electrical activity. Techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) can be used. The cerebellum is a high potential target for neuromodulation of neurological and psychiatric disorders due to the high density of neurons in its superficial layer, its electrical properties, and its participation in numerous closed-loop circuits involved in motor, cognitive, and emotional functions.
Mathias Jucker is a Swiss neuroscientist, Professor, and a Director at the Hertie Institute for Clinical Brain Research of the University of Tübingen. He is also a group leader at the German Center for Neurodegenerative Diseases in Tübingen. Jucker is known for his research on the basic biologic mechanisms underlying brain aging and Alzheimer’s disease.
Steven A. Goldman is an American physician-scientist. His research focuses on the use of stem and progenitor cells for the treatment of neurodegenerative disorders such as Huntington's Disease, as well as for the treatment of glial diseases such as the pediatric leukodystrophies and multiple sclerosis.
The neurovascular unit (NVU) comprises the components of the brain that collectively regulate cerebral blood flow in order to deliver the requisite nutrients to activated neurons. The NVU addresses the brain's unique dilemma of having high energy demands yet low energy storage capacity. In order to function properly, the brain must receive substrates for energy metabolism–mainly glucose–in specific areas, quantities, and times. Neurons do not have the same ability as, for example, muscle cells, which can use up their energy reserves and refill them later; therefore, cerebral metabolism must be driven in the moment. The neurovascular unit facilitates this ad hoc delivery and, thus, ensures that neuronal activity can continue seamlessly.
Saak Victor Ovsepian is an Armenian-Irish neuroscientist best known for his research in neurobiology, neurotherapeutics and translational biosciences. He is a professor in biosciences at the University of Greenwich.
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