Researchers hope to be able to replace dysfunctional brain cells

November 20, 2018, Karolinska Institutet
Bob Harris and Harald Lund at the Department of Clinical Neuroscience.  Credit: Karolinska Institutet

A new study by researchers at Karolinska Institutet supports the theory that replacement of dysfunctional immune cells in the brain has therapeutic potential for neurodegenerative diseases like ALS and Alzheimer's disease. The study, which involved repopulating the brain with new immune cells in an experimental disease model, is published in Nature Communications.

Macrophages are present throughout the body, and are specialised according to the organ in which they operate; in the they are known as . In a healthy brain, microglia are involved in many caretaking functions that support the activities and health of nerve cells. In diseases like ALS and Alzheimer's disease, microglia instead function to harm nerve cells.

New model of microglia depletion

The researchers behind the current study believe that replacement of the dysfunctional microglia with healthy cells will potentially be of therapeutic benefit in such neurodegenerative diseases. Therefore they have developed a new disease model in which the animal's own microglia are removed from the central nervous system (CNS). This leads to a rapid influx of monocytes, precursors of macrophages, into the brain and , giving rise to new microglia-like cells. Microglia in the brain, however, have a different embryonic origin to blood-borne monocytes.

"We knew that blood monocytes would infiltrate the CNS in our experimental mouse model, but we did not know to what degree they would adapt to the new microenvironment," says first author Harald Lund, a recently graduated doctoral student at the Department of Clinical Neuroscience, Karolinska Institutet. "So we dissected the process of repopulation and fully characterised what happened to these cells with time."

Nurture trumps nature

The infiltrating cells adapted to the 'empty' tissue but did not fully differentiate into microglia. However, the monocytes started to express many genes characteristic of microglia, adopted their morphology and exhibited similar functions to microglia. A meta-analysis of several recent studies of microglia repopulation further confirmed the gene signatures as being specific to infiltrating monocytes adapting to the CNS microenvironment, which goes against their nature. The apparent dominance of the tissue microenvironment in dictating cell functionality could be exploited therapeutically, the researchers believe. The study provides support for the ' current projects aiming to develop novel immunotherapies for neurodegenerative diseases.

"There are several incurable in humans, but a complete lack of efficient immunotherapies," says Professor Bob Harris at the Center for Molecular Medicine, Karolinska University Hospital and the Department of Clinical Neuroscience, Karolinska Institutet. "We believe that efficient replacement of dysfunctional microglia has the potential to be an effective therapy, so understanding the molecular events and consequences of repopulation of a microglia-depleted CNS are critical in working towards this goal."

Explore further: New disease model to facilitate development of ALS and MS therapies

More information: Harald Lund et al. Competitive repopulation of an empty microglial niche yields functionally distinct subsets of microglia-like cells, Nature Communications (2018). DOI: 10.1038/s41467-018-07295-7

Related Stories

New disease model to facilitate development of ALS and MS therapies

April 17, 2018
Researchers at Karolinska Institutet in Sweden have developed a new disease model for neurodegenerative diseases such as ALS and MS that can be used to develop new immunotherapies. The model is described in a publication ...

Microglia are key defenders against prion diseases

May 17, 2018
Prion diseases are slow degenerative brain diseases that occur in people and various other mammals. No vaccines or treatments are available, and these diseases are almost always fatal. Scientists have found little evidence ...

Immune cells of the blood might replace dysfunctional brain cells

October 22, 2012
Blood-circulating immune cells can take over the essential immune surveillance of the brain, this is shown by scientists of the German Center for Neurodegenerative Diseases and the Hertie Institute for Clinical Brain Research ...

Regulating microglial activity may reduce inflammation in neurodegenerative diseases

October 17, 2018
A group of Massachusetts General Hospital (MGH) investigators is proposing that targeting immune checkpoints—molecules that regulate the activity of the immune system—in immune cells called microglia could reduce the ...

New test detects tell-tale danger signs in spinal fluid

September 21, 2018
Rare cells resembling those previously thought to exist only in the brain have been discovered in the spinal fluid of HIV patients by using a sensitive new genetic test that could provide insights into a host of neurological ...

Study explains mechanisms behind glioblastoma influence on the immune system

September 12, 2016
Glioblastomas exert an influence on the microglia, immune cells of the brain, which causes them to stimulate cancer growth rather than attacking it. In a study published in the journal Nature Immunology, an international ...

Recommended for you

Biologists identify promising drug for ALS treatment

December 18, 2018
A drug typically used to treat hepatitis could slow the progression of ALS, also known as Lou Gehrig's disease, according to new research by University of Alberta scientists.

Female biology – two X chromosomes and ovaries – extends life and protects mice from aging

December 18, 2018
Around the world, women outlive men. This is true in sickness and in health, in war and in peace, even during severe epidemics and famine. In most animal species, females live longer than males.

Gene variant found in brain complicit in MS onset

December 18, 2018
Multiple sclerosis (MS) is an autoimmune disease affecting the function of the central nervous system. Up to now, most of the 230 genetic variants associated with the disease have been linked to changes in immune cells. However, ...

Sugar targets gut microbe linked to lean and healthy people

December 18, 2018
Sugar can silence a key protein required for colonization by a gut bacterium associated with lean and healthy individuals, according to a new Yale study published the week of Dec. 17 in the journal Proceedings of the National ...

Communication between neural networks

December 18, 2018
The brain is organized into a super-network of specialized networks of nerve cells. For such a brain architecture to function, these specialized networks – each located in a different brain area – need to be able to communicate ...

Get a warrant: Researchers demand better DNA protections

December 18, 2018
New laws are required to control access to medical genetic data by law enforcement agencies, an analysis by University of Queensland researchers has found.

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.