Cocaine On The Brain: Research On Fruit Flies Opens Ground For Therapeutic Impact At Cellular Level

A team of researchers from the Clemson University Centre for Human Genetics have been successful in their discovery of specific brain cell clusters of fruit fly that can be affected by cocaine exposure, opening the way for a contextual framework for future research into a possible drug development to be used in preventing and treating human addictions.

The genetic sensitivity to cocaine is challenging to study despite the drugs neurological effects being known, mainly because of the liable effects of cocaine on the body varying in individuals due to environmental and genetical factors, this discovery opens a leeway into the probable ways to open up to knowing the different genetical sensitivity of the individuals.

Trudy Mackay and Robert Anholt, both Geneticists, in their collaborative research discovered that the use of cocaine instigates a rapid, widespread gene expressional change in the fruit fly brain, with the differences more noticeable in males than females.

In the study, it was also discovered that flies who were exposed to cocaine had increased seizures and impaired movement. All the fly brain cells felt the impact of the drug, most especially the Kenyon cells and some glia cells in the fly’s mushroom bodies. Mushroom bodies are collective brain centres associated with behavioural modifications. Their name was coined from their lookalike pattern to a pair of mushrooms.

Trudy Mackay, one of the researchers and incidentally the director of the Clemson Centre for Human Genetics has this to say about the fly model: “This research identifies the regions of the brain which are important. Now, we can see what genes are expressed when exposed to cocaine and whether there are Federal Drug Administration-approved drugs that could be tested, perhaps first in the fly model. We’ve already spotted several of these genes. This is a baseline. We can now leverage this work to understand potential therapy.”

The Research

The research supported by the National Institute on Drug Abuse had the researchers allowing the male and female flies to take in a fixed amount of sucrose which was supplemented with cocaine for a period of two hours. Their behaviour was observed after the cocaine ingestion and it was seen that they had seizures and compulsive grooming.

To fully take cognizance of the effect of the cocaine ingestion on their gene expression, the brains of the flies were dissected and dissociated into single cells. A sequencing technology was then used to enable libraries of the genes expressed therein for individual cells.

The researchers looked at 88,991 cells in the study, grouping them into 36 distinct cell clusters through the use of cosmopolitan statistical analysis. There was thus a representation of all major cell types–neuronal, glial and other neurotransmitter types in many brain regions, which included mushroom bodies.

Robert Anholt, who partnered Trudy Mackay in the research while analyzing the distinctions between the flies gender said: “We found the effects of cocaine in the brain are very widespread, and there are distinct differences between males and females. There is substantial sexual dimorphism,” said Anholt, Provost’s Distinguished Professor of Genetics and Biochemistry. “We built an atlas of sexually dimorphic cocaine-modulated gene expression in a model brain, which can serve as a resource for the research community.”

How powerful is the single-cell technique?

Researcher Mackay while explaining the single-cell technique ultra-powerfulness with its clear advantage over standard gene expression and impressive advantages over standard gene expression profile studies declared:

“If an entire brain is used and there’s the heterogeneity of gene expression, such that it’s up in one cell and down in another, you don’t see any signal. But with the single-cell analysis, we’re able to capture those very, very fine details that reflect heterogeneity in gene expression among different cell types. It is very exciting to apply this advanced technology here at the CHG,” Mackay explained.

The researchers would definitely explore more possibilities in the genetic technology forte.