New protein regulates water in the brain to control inflammation

"Our study establishes a novel role for a water channel, aquaporin-4, in neuroinflammation, as well as a cell-level mechanism," said Alan S. Verkman, M.D., Ph.D., a senior researcher involved in the work from the Department of Medicine and the Department of Physiology at the University of California, San Francisco. "Our data suggest that inhibition or down-regulation of aquaporin-4 expression in brain and spinal cord may offer a new therapeutic option in diseases such as multiple sclerosis, neuromyelitis optica and other conditions associated with neuroinflammation."

Scientists compared normal mice and mice without genes for producing aquaporin-4 using a model of brain inflammation. These experiments showed significantly reduced brain inflammation in the mice that did not produce aquaporin-4. Researchers then systematically investigated the various possible causes of this reduced neuroinflammation and surprisingly found that aquaporin-4 deletion causes the brain to be less susceptible to inflammation, involving differences in astrocyte reaction to stress. The involvement of aquaporin-4 in brain inflammation provides a new determinant and better understanding of how the brain responses to inflammatory stresses. This suggests that using drugs or other agents that target this protein may be effective for treating a variety of conditions associated with brain or spinal cord inflammation.

"This a new lead in our efforts to stem inflammation in the brain," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The importance of water movement in and out of cells cannot be understated, and this paper helps to clarify what has otherwise been a muddy view of aquaporins."

More information: Lihua Li, Hua Zhang, Michel Varrin-Doyer, Scott S. Zamvil, and A. S. Verkman. Proinflammatory role of aquaporin-4 in autoimmune neuroinflammation. FASEB J May 2011 25:1556-1566; doi:10.1096/fj.10-177279

Provided by Federation of American Societies for Experimental Biology