Researchers identifiy the function of a gene involved in the formation of edemas in the brain

The accumulation of fluids in the brain, what is known as an edema, is a common phenomenon that may be produced as a result of a knock, a heart attack or by developing a cerebral cancer. Moreover, those persons affected by a rare illness called megalencephalicleucoencephalopathy with subcortical cysts (MLC) may also suffer from oedemas. In these cases, the liquid accumulation in the brain is caused by a dysfunction of genetic origin related with the glial cells, which are responsible for maintaining the equilibrium of fluids in the brain because of the production of ion fluxes.

Now, a teamwork headed by Raúl Estévez, a researcher from the University of Barcelona, have established the relationship between the gene GlialCAM —one of the genes whose mutation causes MLC— and the chloridechannel ClC-2, involved in the equilibrium of fluids in the brain. The article of this research has been published in the last issue of the magazine Neuron, and has been commented in a review article and in a summary video also published by this magazine.

Researchers identifiy the function of a gene involved in the formation of edemas in the brain
The mutation of the gene GlialCAM modifies the localization of the chloridechannel in the cells and also alters the function. A) ClC2 localization in cells.

Researchers identifiy the function of a gene involved in the formation of edemas in the brain
B) ClC2 localization modified by gene GlialCAM.

The study shows that the mutation of the gene GlialCAM modifies the localization of the chloridechannel in the cells and also alters the function, which causes water accumulation. According to Estévez, from the Department of Physiological Sciences II of the Faculty of Medicine of the UB, member of the HUBc (Health University of Barcelona Campus), “this result will enable the study of new therapies for patients with MLC leukodystrophy which will be able to be extended to other kinds of oedemas”. Oedema is an important biomedical problem, therefore new strategies which eliminate it should be found. “Working with this rare illness may be useful for finding solutions to a problem that also appears in other more usual illnesses”, states Estévez.
 
The origin of MLC, which has associated symptoms such as epilepsy, mental retardation and autism in some cases, is a leukodystrophy, that is, a degeneration of the myelin that surrounds the neurons (a membrane rich in lipids and cholesterol that acts as an insulator, similarly to the plastic that covers the copper of a cable). From the physiological point of view, myelin helps the transmission of the electrical signal, caused by the ions movement, to be faster. When myelin degenerates, the process of transmission of the signal fails and water accumulates in the brain producing vacuoles.

Science news reference: 
GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl– channel auxiliary subunit.  Jeworutzki, E.; López-Hernández, T.; Capdevila-Nortes, X.; Sirisi, S.; Bengtsson, L.; Montolio, M.; Zifarelli,G.; Arnedo, T.; Muller, C. S.; Schulte,U.; Nunes, V.; Martínez, A.; Jentsch, T. J.; Gasull, X.; Pusch, M.; Estévez, R.  Neuron, March 2012, 73, pages 951-961.DOI 10.1016/j.neuron.2011.12.039
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University of Barcelona