Everyone has seen the ad from the 80’s with a frying pan and an egg, “This is your brain on drugs” and it’s a good analogy. It’s well known that most illegal drugs and even alcohol, can have a negative impact on memory, cognition and motor skills. Cocaine is one of these drugs and a new study shows in detail what happens to the brain when it’s used.
A Johns Hopkins University study published recently showed that high doses of cocaine can cause brain cells to cannibalize themselves. The team also identified a compound of substances that could possibly reverse or prevent the cell toxicity that cocaine inflicts on brain cells.
This compound, dubbed CGP3466B by the Johns Hopkins researchers, could lead to treatment for addicts or be used to protect the brains of children born to cocaine users.
The research was published online in the Proceedings of the National Academy of Sciences.
Using mice for their study, since the mouse brain acts much like the human brain, the team at Hopkins found that when cocaine was administered, there was a significant amount of autophagy in the brain cells. Autophagy is a process where the cells literally digest their own inner parts. Normally it’s a necessary process since it eliminates all debris of the cell as it develops but when it accelerates, as it does when cocaine is used, it results in the death of the cells. The team noted this happening even in the brains of mice whose mothers had been administered doses of cocaine while pregnant.
In a press release from Johns Hopkins Prasun Guha, a postdoctoral fellow and lead author of the paper said, "A cell is like a household that is constantly generating trash. Autophagy is the housekeeper that takes out the trash—it's usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell."
There are three pathways to cell death, autophagy, apoptosis and necrosis. The team started with cell cultures of neurons from mice and tested all of these pathways to see which route cocaine took. Autophagy was the only process that cocaine induced to kill cells.
The next step was to use live mice and see if there was a way to prevent this damage. Guha’s team had a bit of a head start since past studies had shown that nitric oxide, a gas which brain cells use to communicate, and GADPH, an enzyme, were involved in the autophagy process. They also knew that the experimental compound CGP3466B was proven to disrupt nitric oxide/GAPDH interactions. So they tested the compound to see if it could halt the cocaine-induced autophagy. There results were positive and the compound did protect the mice.
While the results are hopeful, much more research is needed both in mice and in human trials. The compound is known to be safe for use in humans as it has been used in clinical trials for Parkinson’s and ALS. It’s use was unsuccessful in treating those diseases.
Check out the video below to learn more about this research and what it could mean for drug treatment and neuroscience.
