Cocaine Induces Neuronal Autophagy

A new study supports the idea that cocaine triggers brain cells to eat themselves and suggests a possible antidote.

By | January 19, 2016

Neurons from a mouse spinal cordFLICKR, NICHD/S. JEONGResearchers have further detailed the mechanism by which high doses of cocaine kill neurons: they cannibalize themselves through the cellular process of autophagy. Examining mouse brains following cocaine administration, Johns Hopkins University neuroscientist Solomon Snyder and his colleagues found evidence that autophagy, in which cells package up various cellular components and debris into vacuoles that merge with enzyme-filled lysosomes for degradation, had spun out of control in neurons, just like previous work has shown for astrocytes and microglia.

“A cell is like a household that is constantly generating trash,” coauthor Prasun Guha, a postdoc in Snyder’s lab, said in a press release. “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.” Guha and colleagues published their results this week (January 18) in PNAS.

The researchers also showed that blocking autophagy using a compound called CGP3466B protects neurons against cocaine-induced cell death. “Since cocaine works exclusively to modulate autophagy versus other cell death programs, there’s a better chance that we can develop new targeted therapeutics to suppress its toxicity,” said coauthor Maged Harraz, a research associate at Johns Hopkins.

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Avatar of: ibap


Posts: 2

January 20, 2016

An interesting study, perhaps, but there is no mention of timing with relation to exposure.  If this had another application, I'd be more impressed.  The full press release says "Snyder says the team hopes its work will eventually lead to treatments that protect adults and infants from the devastating effects of cocaine on the brain."  Do you expect that adults using the drug will also take this compound at the same time?  And if the damage is at the time of exposure, how is this likely to help?  If it has application in other instances of brain damage, then great, but I'd like to see discussion of that as well.

Avatar of: Pilarica


Posts: 1

Replied to a comment from ibap made on January 20, 2016

January 23, 2016

I agree with your posting.  I too, would like to learn more about these findings and research in terms of treatment for someone who used cocaine for over 10 years and who stopped using it about 20 years ago.  Are the toxic effects of cocaine still  active and susceptible to the autophagic processes after 20 years of being "clean"?   The person has been diagnosed with Mild Cognitive Impairment (early Alzheimer's) but we've wondered since the diagnose, a couple of years ago, whether the cocaine is the main culprit, and if so, what can be done to "reverse" the damage, if at all, or to stop any molecular processes, running amock "on pilot" thus inducing and sustaining the autophagy process?

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