Chemogenetics
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.[1] 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.
In recent research projects, chemogenetics has been widely used to understand the relationship between brain activity and behavior. Prior to chemogenetics, researchers used methods such as transcranial magnetic stimulation and deep brain stimulation to study the relationship between neuronal activity and behavior.[2]
Comparison to optogenetics
DREADDs are the most common G protein–coupled receptors used in chemogenetics.[11] These receptors solely get activated by the drug of interest (inert molecule) and influence physiological and neural processes that take place within and outside of the central nervous system.[citation needed]
Chemogenetics has recently been favored over optogenetics, and it avoids some of the challenges of optogenetics. Chemogenetics does not require the expensive light equipment, and therefore, is more accessible. The resolution in optogenetics declines due to light scattering and illuminance declined levels as the distance between the subject and the light source increases. These factors, therefore, don’t allow for all cells to be affected by light and lead to a lower spatial resolution. Chemogenetics, however, does not require light usage and therefore can achieve a higher spatial resolution.[12]
Applications
G-protein coupled receptors' usage and chemogenetics are nowadays the targets for many of the pharmaceutical companies to cure and alleviate symptoms of diseases that involve all tissues of the body.
Recently some studies have considered using a new method called retro DREADDs. This method allows specific neuronal pathways to be studied under cellular resolution. Unlike classic DREADDs, this method is usually used in wild type animals, and these receptors are given to the targeted cells via injection of two viral vectors.[2]
Animal Models
DREADDS have been used in many animal models (e.g., mice and other non-primate animals) to target and influence the activity of various cells. Chemogenetics used in animals assists with demonstrating human disease models such as Parkinson's disease. Having this information allows scientists understand whether viral expression of DREADD proteins, both in-vivo enhancers and inhibitors of neuronal function can be used to bidirectionally affect the behaviors and the activity of the involved neurons. Recent studies have shown that DREADDs were successfully used to treat the motor deficits of rats modeling Parkinson's disease.[15] Other studies have had successes linking the usage of DREADDs and influencing drug seeking and drug sensitization behavior.[14]
The progression of chemogenetics from rodents to non-human primates has been slow due to increased demand in time and expense surrounding these projects. However, some recent studies in 2016 have been able to demonstrate successes showing that silencing the activity of neurons in the orbitofrontal cortex along with the removal of rhinal cortex, restricted the reward task performance in macaques.[16]
Limitation and future directions
Chemogenetics and usage of DREADDs have allowed researchers to advance in biomedical research areas including many