WVU Lab Finds Possible Link to Developmental Brain Disorders

Molecular-level brain study could lead to diagnostic and treatment breakthroughs

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Citations Journal of Neuroscience

Newswise — MORGANTOWN, W.Va. – Researchers in West Virginia University’s Center for Neuroscience have identified a mechanism in brain development that, when disrupted, may play a role in cerebral cortex circuit disorders, including autism, schizophrenia, and childhood epilepsy.

Currently published in the prestigious The Journal of Neuroscience, the study led by Eric Tucker, Ph.D., assistant professor in the Department of Neurobiology and Anatomy, “Cortical Interneurons Require Jnk1 to Enter and Navigate the Developing Cerebral Cortex,” examines how one intracellular signaling pathway affects the movement of cells in a growing brain.

As the most complex and highly evolved part of a mammal’s brain, areas of the cerebral cortex play key roles in not only sensory processing, but higher functions, such as thinking, perceiving, producing, and understanding language.

“Our lab studies genetic mechanisms underlying development of the cerebral cortex, particularly those of inhibitory cortical interneurons,” Dr. Tucker said. “An interneuron is a type of nerve cell that controls activity of the many surrounding neurons it connects to. These cells play vital roles regulating cortical function, and their dysfunction is implicated in serious developmental brain disorders, including autism, schizophrenia, and childhood epilepsy.”

Tucker’s lab identified the c-Jun N-terminal kinase (JNK) signaling pathway to be a critical regulator of the directed movement of cortical interneurons in a mouse’s developing brain, acting as a type of “traffic cop.” When JNK signaling is hampered, migratory interneurons lose their ability to successfully make their way through the cerebral cortex. In short, the cells “get lost” and end up in the wrong places.

A number of factors can interfere with the migration of neurons, including genetics, environmental exposures, and stress. Tucker’s lab will expand upon this research to determine which molecular mechanisms up and down stream of the JNK pathway affect the migration of interneurons, as well as their effects on the final “wiring” and function of the cerebral cortex.

“As we expand on our findings, the data will be essential for eventually translating our basic research into new diagnostic tools and treatment strategies for neurologic and psychiatric diseases,” Tucker added.

Originally published June 4, the article appears on the June 11 cover of The Journal of Neuroscience. To view the cover and access the article’s full text, visit www.jneurosci.org. The accompanying cover video can be seen at http://link.brightcove.com/services/player/bcpid2666468392001?bckey=AQ~~,AAACbMgRO0E~,_GTnRyY88ZaY6C28AhYF8orFcgnUlqsq&bctid=3596600168001.


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