The work to be published in the Journal of Neuroscience also reveals that a drug used in Parkinson’s disease is capable of prevent this damage. By showing how ecstasy can directly compromise such a crucial cellular process the research might help an eventual resolution of the two decade-long debate over whether or not ecstasy use is dangerous.
MDMA (the main component of ecstasy) leads to the production and accumulation of serotonin, a feel-good chemical, which is behind the pleasant effects of the drug. But scientists also know that ecstasy leads to excessive, and most probably toxic quantities of serotonin accumulating in the nerve endings. How this affected ecstasy users, however, was until now not known..
But the Portuguese researchers Ema Alves, Teresa Summavielle, Félix Carvalho and colleagues from the University of Porto and the Porto Polytechnic Institute.
It was known that neurons that produce serotonin eliminate its excess by using monoamine oxidase (MAO), a type of enzyme (enzymes are proteins that mediate chemical reactions) that as it destroys serotonin produces hydrogen peroxide (H2O2). And H2O2 can lead to the formation of free radicals – toxic molecules that when in high quantities can damage the cell components, including DNA, by oxidising them in the same reaction that leads iron to rust. What Alves, Summavielle, Carvalho and colleagues also realised is that in serotonin-producing neurons the existing MAO – which is called MAO-B - is found on the membrane of mitochondria, the structures where nutrients are converted into the energy used by the cell.
Alves and colleagues’ hypothesis was that in these neurons MAO-B, while eliminating the excessive serotonin released in response to ecstasy consume, would produced toxic quantities of free radicals on the mitochondrial membrane. This toxic accumulation could, by affecting the cell energy-producing machine, result in neural death as affected neurons would be incapable of performing basic cellular reactions..
In order to test this hypothesis the team of researchers used four groups of adolescent rats: a group was treated with MDMA, another with MDMA and selegiline – a drug known to block MAO-B activity – and the remaining two served as control. The control groups included one set treated with selegiline alone in order to assure that selegiline had no effect beside MAO-B blocking, and another with an innocuous substance. After some time the animals’ brains were removed and the mitochondria of serotonin-producing neurons analysed. Adolescent rats were used since teenager abusers – ecstasy main users –have particularly vulnerable cerebral and hormonal systems in result of not being yet fully mature.
As hypothesised MDMA-treated rats showed serious damage in their mitochondria including the loss of entire pieces of DNA – mitocondrial DNA codes for proteins involved in the energy-producing process –compromising the whole energetic machine.
On the other hand, animals treated with MDMA and selegiline did not have any signs of mitochondrial problems confirming the importance of MAO-B in MDMA-induced damage. Interestingly, it was seen that MDMA also increase the rats’ body temperature– a hallmark effect of ecstasy – but this was not associated with the mitochondrial damage suggesting that ecstasy was toxic at other levels too.
Ecstasy, or 3,4 methylenedioxymethamphetamine appeared in the raves of the 1980s and although much studied in the last two decades its dangerousness continues to be debated due to the lack of conclusive results. The drug seems to be toxic for neurons (at least in non-humans laboratory models) and has been shown to kill animals but then, relatively few people have died from taking it and those that did it was mostly due to the heatstroke induced by the drug causing respiratory failure. Nevertheless, several studies have suggested that long-term ecstasy users seem to present serious memory loss.
Alves, Summavielle, Carvalho and colleagues’ results reveals a mechanism by which ecstasy leads to “power-cuts” in the brain neurons, compromising their activity and survival. Not only that but this effect was seen in the serotonin-produced neurons and serotonin is known to be involved in memory, which is believed can be compromised by the drug. As consequence the researchers are now investigating if those long-time users of the drug with signs of memory loss show alterations in their mitochondria/serotonin-producing neurons.
Teresa Summavielle, one of the researchers says "We hope that this findings can help convince ecstasy' users, mainly adolescents, that ecstasy really affects the way our brain functions.”
Catarina Amorim | alfa
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy