Nav: Home

Losing neurons can sometimes not be that bad

December 26, 2018

For the first time, scientists at the Champalimaud Centre for the Unknown (CCU), in Lisbon, Portugal, have shown that neuronal cell death in Alzheimer's disease (AD) may actually not be a bad thing - on the contrary, it may be the result of a cell quality control mechanism trying to protect the brain from the accumulation of malfunctioning neurons. Their results, which were obtained using fruit flies that had been genetically modified to mimic the symptoms of human AD, were published in the journal Cell Reports.

The cell quality control mechanism at play is called cell competition. It leads to the selection of the fittest cells in a tissue by enabling a "fitness comparison" between each cell and its neighbors - with the fitter cells then triggering the suicide of less fit ones.

It has been recently shown that cell competition is a normal, powerful anti-aging mechanism in the body in general and in the brain in particular. "In 2015, we discovered that clearing unfit cells from a tissue was a very important anti-aging mechanism to preserve organ function, says Eduardo Moreno, principal investigator of the Cell Fitness lab at the CCU.

His team reasoned that, if these fitness comparisons happened in normal aging, they could also be involved in neurodegenerative diseases associated with accelerated aging, such as Alzheimer's, Parkinson's disease or Huntington's disease, Moreno explains. "This had never been tested", he says. In collaboration with Christa Rhiner's Stem Cells and Regeneration lab at the CCU, they started by testing AD hallmarks in fruit fly models of the disease.

For this, they bred fruit flies that had been genetically manipulated to express in their brain the human amyloid-beta protein, that forms aggregates in the brains of AD patients. The formation of amyloid-β aggregates in the brain is a crucial step in the development of AD.

The transgenic flies displayed symptoms and pathologies similar to those of AD patients: "they showed loss of long-term memory, accelerated aging of the brain and motor coordination problems, all of which got worse with age", specifies Christa Rhiner, whose team studied the cognitive and motor functions of the flies.

The first thing the scientists wanted to do was to see whether in these flies, neuronal death was indeed activated by the process of fitness comparison - in other words, "that the neurons were not dying on their own but being killed by fitter neighbors", Moreno points out.

"When we started, the current view was that neuronal death must be always detrimental. And much to our surprise, we found that neuronal death actually counteracts the disease", says Dina Coelho, first author of the study. What happened was that when she blocked neuronal death in the flies' brain, the insects developed even worse memory problems, worse motor coordination problems, died earlier and their brain degenerated faster.

However, when she boosted the fitness comparison process, thus accelerating the death of unfit neurons, the flies expressing the AD-associated amyloid-beta proteins showed an impressive recovery. "The flies almost behaved like normal flies with regard to memory formation, locomotive behavior and learning", says Rhiner, and this at a time point where the AD flies were already strongly affected.

This means that the anti-aging mechanism in question keeps working well in Alzheimer's disease and shows that, in fact, "the neuronal death protects the brain from more widespread damage and therefore the neuronal loss is not what is bad, it is worse not to let those neurons die", Moreno emphasizes. "Our most important finding is that we have probably been thinking the wrong way about Alzheimer's disease. Our results suggest that neuronal death is beneficial because it removes neurons that are affected by noxious beta-amyloid aggregates from brain circuits, and having those dysfunctional neurons is worse than losing them" Moreno concludes.

The results could have crucial therapeutical implications. "Some molecules have already been identified as potential inhibitors of cell suicide, and some experimental drugs exist, and are being tested which inhibit those inhibitors of cell death, therefore accelerating neuronal death", says Moreno.

But he cautions: "this work has been done in fruit flies". It will be necessary to see, whether these results on neuronal death in Alzheimer's also hold true for humans.
-end-


Champalimaud Centre for the Unknown

Related Neurons Articles:

How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
Neurons that fire together, don't always wire together
As the adage goes 'neurons that fire together, wire together,' but a new paper published today in Neuron demonstrates that, in addition to response similarity, projection target also constrains local connectivity.
Scientists accidentally reprogram mature mouse GABA neurons into dopaminergic-like neurons
Attempting to make dopamine-producing neurons out of glial cells in mouse brains, a group of researchers instead converted mature inhibitory neurons into dopaminergic cells.
More Neurons News and Neurons Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Accessing Better Health
Essential health care is a right, not a privilege ... or is it? This hour, TED speakers explore how we can give everyone access to a healthier way of life, despite who you are or where you live. Guests include physician Raj Panjabi, former NYC health commissioner Mary Bassett, researcher Michael Hendryx, and neuroscientist Rachel Wurzman.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab