Cocaine addiction accelerates aging of the human brain

He brain Humans go through different changes as we age, even in how their DNA is translated. A new study published in the journal Frontiers in psychiatry A study by researchers in Germany and Canada found that these changes can accumulate at a faster rate in people with eating disorders. cocaine use.

Cocaine is a stimulant and addictive drug made from the leaves of the coca plant, native to South America. More than 21 million people consumed this psychostimulant worldwide in 2020. Over the past decade, the hospitalization rate has increased.

When consumed, cocaine increases levels of dopaminea natural chemical messenger, or neurotransmitter, in brain circuits involved in movement control and reward.

The reward circuitry adapts over time to the extra dopamine generated by cocaine and gradually becomes less sensitive to its presence. The result is that people start taking higher and higher doses, according to the National Institute on Drug Abuse in the US.

Cocaine is one of the most addictive substances. It interferes with the brain’s reward pathways, forcing its cells to continue emitting pleasurable signals until the drug wears off. According to US estimates, one in five people who use cocaine eventually develop an addiction.

Scientists tend to think of drug addiction as a disease of the brain. When you enjoy sex, food, music, or other activities, brain regions along the reward pathway are flooded with pleasure-inducing dopamine. The use of drugs like cocaine copies this effect, but up to ten times more intensely.

However, healthy brains aren’t at the mercy of these dopamine rushes: In them, the prefrontal cortex weighs the options and can decide to forego pleasurable activities when the time or place isn’t right. On the contrary, this “inhibitory control” is altered in the addict’s brain, which makes resistance more difficult.

But what are the biochemical changes in the prefrontal cortex that cause this deterioration?

German and Canadian scientists have demonstrated through the study that, in humans, cocaine use disorder causes changes in the “methylome” of a subregion of the prefrontal cortex of the brain, area 9 by Brodman. This is a part considered important for self-awareness and inhibitory control.

Normally, a higher degree of DNA methylation leads to the “knockdown” of neighboring genes. DNA methylation is an important mechanism for regulating gene expression.

“The identified alterations in DNA methylation could contribute to functional changes in the human brain and thus to behavioral aspects associated with addiction,” said first author Eric Poisel, a doctoral student at the Central Institute for Mental Health. from Mannheim, Germany.

Because brain methylome research is invasive, the study was conducted in cryopreserved brains from 42 deceased male donors, half of whom had suffered from a cocaine use disorder and the other half had not. This is important, because most of the previous studies in this area have been done on rat brains.

The researchers found evidence that Brodmann area 9 cells appear biologically “older” in people with cocaine use disorders. This shows that these cells age faster than in people without substance use disorders.

To find out, they used DNA methylation patterns as a measure of the biological age of cells in Brodmann’s area 9. The biological age of cells, tissues, and organs can be older or younger than their chronological age, depending on diet, lifestyle, and exposure to disease or harmful environmental factors. Scientists can thus estimate biological age from methylome data with established mathematical algorithms.

“We detected a trend towards greater biological aging of the brain in people with cocaine use disorder compared to people without cocaine use disorder. This could be due to pathological processes related to cocaine in the brain, such as inflammation or cell death,” explained co-author Stephanie Witt, a researcher at the same institute where Poisel works.

“As the estimate of the biological age is a very recent concept in addiction research and is influenced by many factors, further studies are needed to investigate this phenomenon, with larger sample sizes than could be done here,” he commented. .

Poisel and colleagues also analyzed differences in the degree of methylation at 654,448 sites in the human genome, looking for associations with the presence or absence of cocaine use disorders over each donor’s lifetime. . They corrected for differences in donor age, time since death, brain pH, and other conditions such as depressive disorder and alcohol use disorder.

They found 17 genomic regions that were more methylated in donors with cocaine use disorders than in donors without, and three less methylated regions in donors with the disorder.

“We were surprised that in our network analysis, changes in DNA methylation were particularly prominent among genes that regulate neuron activity and connectivity between neurons,” Poisel said. He suggested that further studies will be needed to dig deeper into the findings.

“Furthermore, it was fascinating that among the genes that showed the most pronounced changes in DNA methylation levels in our study, two genes regulated behavioral aspects of cocaine use in the rodent experiments” , noted Witt.

Short-term effects of cocaine use are known to include extreme energy and happiness, mental alertness, hypersensitivity to light, sound and touch, irritability, paranoia (extreme and unwarranted distrust towards others).

Some of the long-term effects of cocaine depend on the method of use, according to the National Institute on Drug Abuse. If inhaled, it can cause loss of smell, nosebleeds, frequent runny nose, and swallowing problems.

If cocaine is smoked, it can cause coughing, asthma, shortness of breath and an increased risk of illnesses such as pneumonia. If ingested by mouth, it can cause marked damage to the intestine due to reduced blood flow.

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