Protein makes brain-damper ready for use

Claudin5a guarantees expansion of cerebral chambers

The loss of Claudin5a prevents the normal expansion of brain ventricles in the zebrafish embryo. They thus only reach about one third of the normal size. The cerebral ventricle shown here is marked with the indicator fluid sodium green and shown in orange in a false color. © Jin Jing Zhang / MDC
Read out

Fluid-filled brain chambers, like shock absorbers, absorb shock or shock and protect the brain. Berlin researchers have now shown in zebrafish how these chambers form before the blood-brain barrier. A particular protein is crucial. It forms a barrier between the nerve cell tissue and the chambers.

Absent Claudin5a, the chambers can not expand and the formation of the brain is disturbed. These findings could be used to test drug permeability to the brain, according to researchers in the Proceedings of the National Academy of Sciences (PNAS).

Insulated brain chambers

Like the blood-brain barrier, which prevents pathogens from entering the brain via the blood, the cerebral ventricles or brain ventricles are also isolated from their environment. Thus, the chambers can fill with fluid, expand and thus contribute to the stability of the brain.

In contrast to the blood-brain barrier, the barrier responsible for this does not contain any blood vessels, but consists exclusively of nerve cells, which, however, are also firmly bound together by protein threads. One component of these tightly knotted threads, the tight junctions, is the protein Claudin5a.

Protein function decoded

Researchers led by Jingjiing Zhang from the Max Delbrück Center (MDC) and the Leibniz Institute of Molecular Pharmacology (FMP) in Berlin have now decrypted the function of this protein at a very early stage of zebrafish development. In their experiments they were able to show that the chambers do not expand when claudin5a is absent. The result: the shape of the brain is changed. display

However, when the researchers restored the function of Claudin5a by switching on Claudin5a throughout the embryo, the cerebral chambers were able to expand again.

The scientists are convinced that this knowledge about the tightness of barriers by Claudin5 can also be used for pharmacological research. Drugs hardly or not at all cross the blood-brain barrier, which makes the treatment of brain diseases difficult.

Researchers want to switch off Claudin5a - at short notice

ZIn the zebrafish, one could investigate which substances temporarily deactivate the function of Claudin5a and thus contribute to the opening of brain barriers such as the blood-brain barrier. This could be important for the development of drugs that work in the brain, "Dr. Salim Seyfried from the MDC.

(idw - Max Delbrøck Center for Molecular Medicine (MDC), 07.01.2010 - DLO)