Disrupted fat breakdown in the brain makes mice dumb

May 19, 2017
Disrupted fat breakdown in the brain makes mice dumb
Healthy control nerve cells with intact “garbage bags” (red). Credit: AG van Echten-Deckert/Uni Bonn

A study led by the University of Bonn opens a new perspective with regard to the development of dementia. The scientists blocked the breakdown of a certain fat molecule in the mouse brain. As a result the animals exhibited learning and memory problems. Also, the quantity of Alzheimer-specific proteins in their brains increased significantly. The researchers now have a clue as to why the mice become dumb. The results are published in the renowned scientific journal "Autophagy".

Apart from water, our brain is rich in lipids – in plain language: fats. The lipids act, for instance, as an insulating layer around the nerve fibers and thus prevent short circuits. However, they are also a main component in the delicate membranes that surround the brain cells.

Sphingolipids, a special lipid type are highly enriched in the brain. One of their degradation products, S1P, may play a central role in the development of Alzheimer's and other forms of dementia. "We raised mice that are no longer able to break down S1P in large parts of their brain," explains Dr. Gerhild van Echten-Deckert. "The animals then displayed severely reduced learning and memory performance."

Van Echten-Deckert undertakes research at the LIMES Institute at the University of Bonn (the acronym stands for "Life and Medical Sciences") as an assistant professor. For a long time, she has been one of the few experts in the world interested in the role of S1P in the brain. The new study could fundamentally change this, as the researchers at the University of Bonn, Jena University Hospital, the German Center for Neurodegenerative Diseases (DZNE) and from San Francisco and Madrid were able to show what far-reaching consequences disrupted S1P breakdown has.

"Self-eating" keeps the brain healthy

Nerve cells with disrupted S1P breakdown: the yellow-orange marked garbage bags have not closed properly, and are therefore transparent. Credit: AG van Echten-Deckert/Uni Bonn

Normally, S1P is broken down into simpler products. One such breakdown product generated is important for a vital metabolic pathway – called autophagy. The word autophagy (literally translates to "self-eating") and the pathway enables cells to digest and recycle their own components. The cells are thus cleared from defective proteins and cell organelles that no longer function properly.

Intracellular waste disposal works in two steps: first, it packs the waste in tiny "". These then merge with other "bags" that contain highly reactive enzymes. The enzymes "shred" the content of the garbage bags and thus dispose it off.

The break-down product of S1P is involved in packing the waste into the intracellular garbage bags. "If S1P is not broken down, fewer closed garbage bags are formed; autophagy then no longer works accurately," explains the first author of the study Daniel Mitroi, who has recently completed his PhD at the LIMES Institute. "Harmful substances thus accumulated in the brains of our mice. These included the protein APP, which plays a key role in the development of Alzheimer's."

As autophagy is crucial for normal functioning of the brain, improper intracellular waste disposal results in severe illnesses. Therefore last year the Nobel Prize in Medicine was awarded to the Japanese scientist Yoshinori Ohsumi for his notable work on this vital mechanism. The results of the current study shed light on a previously overlooked mechanism for dementia development. "In the long term, our work may contribute towards developing successful treatment strategies for disorders," says Dr. van Echten-Deckert.

Explore further: Cells' garbage disposal may hold key to healthier life

More information: Daniel N. Mitroi et al. SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production, Autophagy (2017). DOI: 10.1080/15548627.2017.1291471

Related Stories

Cells' garbage disposal may hold key to healthier life

October 3, 2016
Autophagy, the little-understood method by which human cells dispose of harmful waste and unwelcome intruders, may one day be central to therapies for longer, healthier living, experts said.

Taking out the cellular 'trash'—at the right place and the right time

October 20, 2016
New insight about how cells dispose of their waste is now given by the group of Claudine Kraft at the Max F. Perutz Laboratories (MFPL) of the University of Vienna. They show the necessity of a regulation in space and time ...

The benefits of a spotless mind

November 15, 2013
Alzheimer's disease is an age-related memory disorder characterized by the accumulation of clumps of the toxic amyloid-β (Aβ) protein fragment in the extracellular space around neurons in the brain. Drugs that help to 'clean ...

Cell disposal faults could contribute to Parkinson's, study finds

January 24, 2017
A fault with the natural waste disposal system that helps to keep our brain cell 'batteries' healthy may contribute to neurodegenerative disease, a new study has found.

Discovery of novel autophagy regulators for treatment of neurodegenerative diseases

February 17, 2017
A research team led by Professor Li Min, Director of the Teaching and Research Division (CMTR), and Director of the Mr and Mrs Ko Chi Ming Centre for Parkinson's Disease Research under the School of Chinese Medicine (SCM) ...

Role for autophagic cellular degradation process in maintaining genomic stability

November 29, 2016
Centrosomes play an essential role in cell division by organizing the protein framework on which chromosomes assemble and then separate prior to division into daughter cells. Centrosomes are made up of a pair of centrioles, ...

Recommended for you

Scientists find key to regenerating blood vessels

November 23, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.