 | This article needs more reliable medical references for verification or relies too heavily on primary sources .(January 2024) |  |
Magnetogenetics is a medical research technique whereby magnetic fields are used to affect cell function. [1]
| This article needs more reliable medical references for verification or relies too heavily on primary sources .(January 2024) | |
Magnetogenetics is a medical research technique whereby magnetic fields are used to affect cell function. [1]
The development of genetic technologies that can modulate cellular processes has greatly contributed to biological research. A representative example is the development of optogenetics, which is a neuromodulation tool kit that involves light-sensitive proteins such as opsins. This progress provided the grounds for a breakthrough in linking the causal relationship between neuronal activity and behavioral outcome.
The foremost strength of the genetic toolkits used in neuromodulation is that it can provide either spatially or temporally, or both, precise modulation of the brain nervous system. To date, several technologies are adapted with genetics (e.g. optogenetics, chemogenetics, etc.), and each technology has strengths and limits. For example, optogenetics has advantages in that it can provide temporally and spatially precise manipulation of neurons. On the other hand, it involves light stimulation, which cannot penetrate tissues effectively and requires implanted optical devices, limiting its applications for in vivo live animal studies
Techniques that rely on the magnetic control of cellular process are relatively new. This technique may provide an approach that does not require implantation of invasive electrodes or optical devices. This method will allow penetration in to the deeper region of the brain, and may have lower response latency. [2] In 1980, Young and colleagues have shown that magnetic fields with magnitudes in millitesla range are able to penetrate into the brain without attenuation of the signal or side effects because of the negligible magnetic susceptibility and low conductivity of biological tissue. [3] Early attempts to manipulate electrical signaling within brain using magnetic fields was performed by Baker et al., who later developed devices for transcranial magnetic stimulation (TMS) in 1985.
To apply magnetogenetics in biological and neuroscientific research, fusing TRPV class receptors with a paramagnetic protein (typically ferritin) was suggested. These paramagnetic proteins, which typically contain iron or have iron-containing cofactors, are then magnetically stimulated. How this technique can modulate neuronal activity remains unclear but it is thought that the ion channels are activated and opened either by mechanical force exerted by the paramagnetic proteins, or by heating of these via magnetic stimulation. However, availability of such paramagnetic proteins as a transducer for magnetic field to mechanical or temperature stimuli is controversial.
On the other hand, nanoparticles have been suggested as possible candidates that can function as the transducer of magnetic field to the stimulus cue. Based on this concept, next generation of magnetogenetics technique is being developed. In 2010, Arnd Pralle and colleges showed that the first in vivo magneto-thermal stimulation of heat sensitive ion channel TRPV1 that employs magnetic nanoparticles as a transducer in C. elegans. [4] In 2012, Seung Chan Kim showed gene expression profile change of total human genome approximately 30,000 genes using 0.2T static magnetic fields. [5] In 2015, Polina Anikeeva's research group demonstrated that similar concept can enhance the neuronal signals in mammalian brain. [6] In 2021, Jinwoo Cheon's research group has successfully developed the magneto-mechanical genetics which uses magnetic stimulation derived mechanical force in mammalian. [7] In this study, magnetic torque by rotating magnetic field was employed to activate the mechanosensitive cation channel Piezo1. Results of this study show that remote, in vivo manipulation of behavior of mice can be done using magnetogenetics. Cheon's group further developed a magnetogenetic system enables cell-type-specific modulation of deep brain neural circuits. [8] This was achieved by combining Piezo1 ion channels and Cre-loxP technology, allowing precise, reversible, and wireless control of neuronal activity in freely moving animals. The study demonstrated significant potential for neuroscience research by demonstrating several applications such as feeding behavior modulation, long-term obesity control, and social interaction studies. This torque-based system developed by Cheon is anticipated to be valuable not only for neuroscience research but also for various deep tissue in vivo applications and therapeutics.
One of the main issues in magnetogenetics is related the physical properties of the ferritin. [9] The ferritin is composed of 24 subunits of protein complex and a small iron oxide core. The core of the ferritin is in the form of ferric hydroxide which has antiferromagnetic properties. Some researchers have reported that ferritin has remnant magnetization due to their intrinsic defect and impurities. [10] However, even with optimistic calculations, the magnetic interaction energy for heat or force generation is several orders below than thermal fluctuation energy. Recently, other researchers hypothesized that there are other possible mechanisms for activate the ion channels, but these studies remain inconclusive.
In haemodynamics, the body must respond to physical activities, external temperature, and other factors by homeostatically adjusting its blood flow to deliver nutrients such as oxygen and glucose to stressed tissues and allow them to function. Haemodynamic response (HR) allows the rapid delivery of blood to active neuronal tissues. The brain consumes large amounts of energy but does not have a reservoir of stored energy substrates. Since higher processes in the brain occur almost constantly, cerebral blood flow is essential for the maintenance of neurons, astrocytes, and other cells of the brain. This coupling between neuronal activity and blood flow is also referred to as neurovascular coupling.
Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity.
Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.
Photostimulation is the use of light to artificially activate biological compounds, cells, tissues, or even whole organisms. Photostimulation can be used to noninvasively probe various relationships between different biological processes, using only light. In the long run, photostimulation has the potential for use in different types of therapy, such as migraine headache. Additionally, photostimulation may be used for the mapping of neuronal connections between different areas of the brain by “uncaging” signaling biomolecules with light. Therapy with photostimulation has been called light therapy, phototherapy, or photobiomodulation.
Neural engineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.
Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion channels include voltage-gated ion channels, ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels have been synthesized in the laboratory for study, although two naturally occurring examples, channelrhodopsin and anion-conducting channelrhodopsin, are currently known. Photoreceptor proteins, which act in a similar manner to light-gated ion channels, are generally classified instead as G protein-coupled receptors.
Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene. KCNK4 protein channels are also called TRAAK channels.
Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient with Retinitis pigmentosa.
Nonsynaptic plasticity is a form of neuroplasticity that involves modification of ion channel function in the axon, dendrites, and cell body that results in specific changes in the integration of excitatory postsynaptic potentials and inhibitory postsynaptic potentials. Nonsynaptic plasticity is a modification of the intrinsic excitability of the neuron. It interacts with synaptic plasticity, but it is considered a separate entity from synaptic plasticity. Intrinsic modification of the electrical properties of neurons plays a role in many aspects of plasticity from homeostatic plasticity to learning and memory itself. Nonsynaptic plasticity affects synaptic integration, subthreshold propagation, spike generation, and other fundamental mechanisms of neurons at the cellular level. These individual neuronal alterations can result in changes in higher brain function, especially learning and memory. However, as an emerging field in neuroscience, much of the knowledge about nonsynaptic plasticity is uncertain and still requires further investigation to better define its role in brain function and behavior.
Biomagnetics is a field of biotechnology. It has actively been researched since at least 2004. Although the majority of structures found in living organisms are diamagnetic, the magnetic field itself, as well as magnetic nanoparticles, microstructures and paramagnetic molecules can influence specific physiological functions of organisms under certain conditions. The effect of magnetic fields on biosystems is a topic of research that falls under the biomagnetic umbrella, as well as the construction of magnetic structures or systems that are either biocompatible, biodegradable or biomimetic. Magnetic nanoparticles and magnetic microparticles are known to interact with certain prokaryotes and certain eukaryotes.
Karl Alexander Deisseroth is an American scientist. He is the D.H. Chen Foundation Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.
Cheon Jinwoo is the H.G. Underwood Professor at Yonsei University and the Founding Director of the Center for Nanomedicine, Institute for Basic Science (IBS). As a leading chemist in inorganic materials chemistry and nanomedicine Cheon and his research group mainly focus on developing chemical principles for synthesizing complex inorganic materials and nanoprobes/actuators used in imaging and controlling of cellular functions within the deep tissue in living systems.
Neuromodulation is "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body". It is carried out to normalize – or modulate – nervous tissue function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli such as a magnetic field (rTMS), an electric current, or a drug instilled directly in the subdural space. Emerging applications involve targeted introduction of genes or gene regulators and light (optogenetics), and by 2014, these had been at minimum demonstrated in mammalian models, or first-in-human data had been acquired. The most clinical experience has been with electrical stimulation.
Gene therapy is being studied for some forms of epilepsy. It relies on viral or non-viral vectors to deliver DNA or RNA to target brain areas where seizures arise, in order to prevent the development of epilepsy or to reduce the frequency and/or severity of seizures. Gene therapy has delivered promising results in early stage clinical trials for other neurological disorders such as Parkinson's disease, raising the hope that it will become a treatment for intractable epilepsy.
Chemogenetics is the process by which macromolecules can be engineered to interact with previously unrecognized small molecules. Chemogenetics as a term was originally coined to describe the observed effects of mutations on chalcone isomerase activity on substrate specificities in the flowers of Dianthus caryophyllus. This method is very similar to optogenetics; however, it uses chemically engineered molecules and ligands instead of light and light-sensitive channels known as opsins.
Anion-conducting channelrhodopsins are light-gated ion channels that open in response to light and let negatively charged ions enter a cell. All channelrhodopsins use retinal as light-sensitive pigment, but they differ in their ion selectivity. Anion-conducting channelrhodopsins are used as tools to manipulate brain activity in mice, fruit flies and other model organisms (Optogenetics). Neurons expressing anion-conducting channelrhodopsins are silenced when illuminated with light, an effect that has been used to investigate information processing in the brain. For example, suppressing dendritic calcium spikes in specific neurons with light reduced the ability of mice to perceive a light touch to a whisker. Studying how the behavior of an animal changes when specific neurons are silenced allows scientists to determine the role of these neurons in the complex circuits controlling behavior.
Polina Olegovna Anikeeva is a Russian-born American materials scientist who is a Professor of Material Science & Engineering as well as Brain & Cognitive Sciences at the Massachusetts Institute of Technology (MIT). She also holds faculty appointments in the McGovern Institute for Brain Research and Research Laboratory of Electronics at MIT. Her research is centered on developing tools for studying the underlying molecular and cellular bases of behavior and neurological diseases. She was awarded the 2018 Vilcek Foundation Prize for Creative Promise in Biomedical Science, the 2020 MacVicar Faculty Fellowship at MIT, and in 2015 was named a MIT Technology Review Innovator Under 35.
Nanoneuroscience is an interdisciplinary field that integrates nanotechnology and neuroscience. One of its main goals is to gain a detailed understanding of how the nervous system operates and, thus, how neurons organize themselves in the brain. Consequently, creating drugs and devices that are able to cross the blood brain barrier (BBB) are essential to allow for detailed imaging and diagnoses. The blood brain barrier functions as a highly specialized semipermeable membrane surrounding the brain, preventing harmful molecules that may be dissolved in the circulation blood from entering the central nervous system.
Fiber photometry is a calcium imaging technique that captures 'bulk' or population-level calcium (Ca2+) activity from specific cell-types within a brain region or functional network in order to study neural circuits Population-level calcium activity can be correlated with behavioral tasks, such as spatial learning, memory recall and goal-directed behaviors. The technique involves the surgical implantation of fiber optics into the brains of living animals. The benefits to researchers are that optical fibers are simpler to implant, less invasive and less expensive than other calcium methods, and there is less weight and stress on the animal, as compared to miniscopes. It also allows for imaging of multiple interacting brain regions and integration with other neuroscience techniques. The limitations of fiber photometry are low cellular and spatial resolution, and the fact that animals must be securely tethered to a rigid fiber bundle, which may impact the naturalistic behavior of smaller mammals such as mice.