Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A ticking time bomb: Circulating anti-NMDA receptor autoantibodies

23.09.2013
Scientists of the CNMPB and of the Max Planck Institute of Experimental Medicine find NMDAR autoantibodies in 10% of all tested individuals, which can cause neuropsychiatric dysfunctions in case of blood brain barrier disturbance. The study has been recently published in the journal Molecular Psychiatry.

“Anti-NMDA receptor encephalitis” was the name given to an acute brain disease, whose potential cause and treatment has been described in a number of recent publications. On the molecular level, this acute form of encephalitis is attended by a reduced function of glutamate receptors (NMDAR), which is caused by autoantibodies against these receptors in the brain.

Symptoms of the disease can be psychosis, movement disorders, epileptic seizures or reduction of cognitive performance in various shapes. However, as most studies are based on a generally fairly small number of patients, they neither cast a light on the relevance of NMDAR autoantibodies in the blood for the pathogenesis of the disease, nor do they yield data about their prevalence in healthy individuals.

Notable new findings are now provided by a new study conducted by Prof. Hannelore Ehrenreich and her team in cooperation with the Göttingen DFG Research Center and Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB).

The study demonstrates for the first time that NMDAR autoantibodies can be found in the serum of more than 10% of a total of nearly 3000 tested individuals, irrespective of whether they are patients or healthy individuals. Surprisingly, comparable autoantibody titers, antibody classes and functionalities were detected in healthy subjects and patients with a neuropsychiatric disease.

This insight led the authors of the study to the following central question: If, in fact, these autoantibodies play some pathological role, why do healthy individuals bearing them stay healthy?

In a series of animal experiments the scientists could demonstrate that the prerequisite for a triggering of symptoms by these autoantibodies, and thus for the pathogenesis of a disease process, is a dysfunction of the blood-brain barrier. This physiological barrier in a healthy organism delimits the central nervous system like a filter from the general blood stream and thus protects it from circulating pathogenic agents and toxins. A disruption of its natural barrier function enables the NMDAR autoantibodies circulating in the blood to enter the brain. This way, they reach the NMDA receptors located in the brain and can cause an impairment of function resulting in psychosis-similar symptoms, epileptic seizures or cognitive dysfunctions.

"In other words, more than 10% of all individuals carry a 'ticking time bomb', the disease relevance of which is only suppressed by an intact blood-brain barrier“, remarks Prof. Ehrenreich. An impaired blood brain barrier can be caused by a stroke, a brain trauma or by a viral infection, amongst others. In this context, the scientists performed an additional retrospective evaluation based on a large cohort of patients. They demonstrate an increase in the severity of neurological symptoms in subjects with a temporary or persisting blood-brain barrier dysfunction who carry NMDAR autoantibodies in their serum.

The authors of the study for the first time examined the question which factors are, in the end, responsible for triggering the generation of these NMDA autoantibodies. They found, on the one hand, an association of past influenza A or B infections with the appearance of these autoantibodies; on the other hand they identified by means of a genome-wide association study a genetic risk factor related to NMDAR biology.

The study published by first author Christian Hammer and coworkers is not only conceptually novel, it also yields considerable insight into a pathophysiological mechanism that is of crucial importance for neuropsychiatry and also for other clinical disciplines. The scientists commend that “patients with acute or chronic impairment of the blood-brain-barrier, e.g. after a brain injury, a stroke, any kind of encephalitis, epilepsy and also multiple sclerosis should be screened for the presence of NMDAR autoantibodies”. This might contribute to improve the course of disease by appropriate therapeutic methods and prevent long-term complications.

(cnmpb/mpiem)

Contact:
Max Planck Institute of Experimental Medicine
Clinical Neuroscience
Prof. Dr. Hannelore Ehrenreich (ehrenreich@em.mpg.de)
Phone 0551 / 39-3899 615
Hermann-Rein-Str. 3., 37075 Göttingen, Germany
Weitere Informationen:
http://www.ncbi.nlm.nih.gov/pubmed/23999527
- Original Publication
http://www.em.mpg.de/index.php
- Max Planck Institute of Experimental Medicine
http://www.cnmpb.de
- Cluster of Excellence and DFG-Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)

Dr. Heike Benecke | idw
Further information:
http://www.em.mpg.de/index.php

More articles from Life Sciences:

nachricht During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>