Understanding How Stress Triggers Ataxia

Research Brief

Understanding How Stress Triggers Ataxia

Cuerpo

Stress is one of the most common triggers of episodic neurological disorders such as migraine epilepsy, and several types of movement disorders. But precisely how stress triggers such episodes has been a mystery.  

In a study published online on April 20 in Science Advances, Kamran Khodakhah, Ph.D., and colleagues used a mouse model of a human episodic neurologic disorder called episodic ataxia type 2 to address the issue. The researchers found that acute stress initiates episodic attacks by activating α1 adrenergic receptors on Purkinje cells, which are found in the brain’s cerebellum and play key roles in controlling motor movement. Activating those receptors causes Purkinje cells to fire erratically, leading to abnormal movement. In addition, by affecting a casein kinase II-dependent signaling pathway in Purkinje cells, stress disrupts the pacemaking within those cells that is essential for motor coordination. Administering silmitasertib—a casein kinase II inhibitor approved for treating certain types of cancer—prevented stress-induced attacks in the mice. The findings suggest α1 adrenergic receptors and casein kinase II are potential targets for drugs aimed at preventing stress from triggering attacks in susceptible people.

Dr. Khodakhah is professor in the Dominick P. Purpura Department of Neuroscience, of psychiatry and behavioral sciences and in the Saul R. Korey Department of Neurology, and the Florence and Irving Rubinstein Chair in Neuroscience at Einstein.