1. Amrutbhai Savasya, scavenger caste, Gujarat, 2002
2. Woman in a rock quarry, Bihar, 2002
3. Boy playing, Bihar, 2002
4. Untouchable midwife with discarded baby, Bihar, 2002
5. Street Market in Untouchable neighborhood, Mumbai, 2002
6. Laxman Singh, Rajasthan, 2002
7. Ramprasad and Ramlakhan, Uttar Pradesh, 2002
8. Child of the Dhobi caste, Yamuna River, Delhi, 2002
szimbiózisban élünk. <3
As the human body fine-tunes its neurological wiring, nerve cells often must fix a faulty connection by amputating an axon — the “business end” of the neuron that sends electrical impulses to tissues or other neurons. It is a dance with death, however, because the molecular poison the neuron deploys to sever an axon could, if uncontained, kill the entire cell.
Researchers from the University of North Carolina School of Medicine have uncovered some surprising insights about the process of axon amputation, or “pruning,” in a study published May 21 in the journal Nature Communications. Axon pruning has mystified scientists curious to know how a neuron can unleash a self-destruct mechanism within its axon, but keep it from spreading to the rest of the cell. The researchers’ findings could offer clues about the processes underlying some neurological disorders.
“Aberrant axon pruning is thought to underlie some of the causes for neurodevelopmental disorders, such as schizophrenia and autism,” said Mohanish Deshmukh, PhD, professor of cell biology and physiology at UNC and the study’s senior author. “This study sheds light on some of the mechanisms by which neurons are able to regulate axon pruning.”
Axon pruning is part of normal development and plays a key role in learning and memory. Another important process, apoptosis — the purposeful death of an entire cell — is also crucial because it allows the body to cull broken or incorrectly placed neurons. But both processes have been linked with disease when improperly regulated.
The research team placed mouse neurons in special devices called microfluidic chambers that allowed the researchers to independently manipulate the environments surrounding the axon and cell body to induce axon pruning or apoptosis.
They found that although the nerve cell uses the same poison — a group of molecules known as Caspases — whether it intends to kill the whole cell or just the axon, it deploys the Caspases in a different way depending on the context.
“People had assumed that the mechanism was the same regardless of whether the context was axon pruning or apoptosis, but we found that it’s actually quite distinct,” said Deshmukh. “The neuron essentially uses the same components for both cases, but tweaks them in a very elegant way so the neuron knows whether it needs to undergo apoptosis or axon pruning.”
In apoptosis, the neuron deploys the deadly Caspases using an activator known as Apaf-1. In the case of axon pruning, Apaf-1 was simply not involved, despite the presence of Caspases. “This is really going to take the field by surprise,” said Deshmukh. “There’s very little precedent of Caspases being activated without Apaf-1. We just didn’t know they could be activated through a different mechanism.”
In addition, the team discovered that neurons employ other molecules as safety brakes to keep the “kill” signal contained to the axon alone. “Having this brake keeps that signal from spreading to the rest of the body,” said Deshmukh. “Remarkably, just removing one brake makes the neurons more vulnerable.”
Deshmukh said the findings offer a glimpse into how nerve cells reconfigure themselves during development and beyond. Enhancing our understanding of these basic processes could help illuminate what has gone wrong in the case of some neurological disorders.
Results of the study at Imperial College London, parts of which were televised in Drugs Live on Channel 4 in 2012, have now been published in the journal Biological Psychiatry.
The findings hint at ways that ecstasy, or MDMA, might be useful in the treatment of anxiety and post-traumatic stress disorder (PTSD).
MDMA has been a popular recreational drug since the 1980s, but there has been little research on which areas of the brain it affects. The new study is the first to use functional magnetic resonance imaging (fMRI) on resting subjects under its influence.
Twenty-five volunteers underwent brain scans on two occasions, one after taking the drug and one after taking a placebo, without knowing which they had been given.
The results show that MDMA decreases activity in the limbic system – a set of structures involved in emotional responses. These effects were stronger in subjects who reported stronger subjective experiences, suggesting that they are related.
Communication between the medial temporal lobe and medial prefrontal cortex, which is involved in emotional control, was reduced. This effect, and the drop in activity in the limbic system, are opposite to patterns seen in patients who suffer from anxiety.
MDMA also increased communication between the amygdala and the hippocampus. Studies on patients with PTSD have found a reduction in communication between these areas.
The project was led by David Nutt, the Edmond J. Safra Professor of Neuropsychopharmacology at Imperial College London, and Professor Val Curran at UCL.
Dr Robin Carhart-Harris from the Department of Medicine at Imperial, who performed the research, said: “We found that MDMA caused reduced blood flow in regions of the brain linked to emotion and memory. These effects may be related to the feelings of euphoria that people experience on the drug.”
Professor Nutt added: “The findings suggest possible clinical uses of MDMA in treating anxiety and PTSD, but we need to be careful about drawing too many conclusions from a study in healthy volunteers. We would have to do studies in patients to see if we find the same effects.”
MDMA has been investigated as an adjunct to psychotherapy in the treatment of PTSD, with a recent pilot study in the US reporting positive preliminary results.
As part of the Imperial study, the volunteers were asked to recall their favourite and worst memories while inside the scanner. They rated their favourite memories as more vivid, emotionally intense and positive after MDMA than placebo, and they rated their worst memories less negatively. This was reflected in the way that parts of the brain were activated more or less strongly under MDMA. These results were published in the International Journal of Neuropsychopharmacology.
Dr Carhart-Harris said: “In healthy volunteers, MDMA seems to lessen the impact of painful memories. This fits with the idea that it could help patients with PTSD revisit their traumatic experiences in psychotherapy without being overwhelmed by negative emotions, but we need to do studies in PTSD patients to see if the drug affects them in the same way.”