Sat., 3:15 p.m., Walter E. Washington Convention Center, 150A
Lindsay Hayes and Akira Sawa
A Blood Pressure Hormone Implicated in Psychosis
In an effort to find a marker that predicts psychosis, postdoctoral researcher Lindsay Hayes, Ph.D., learned unexpectedly that mice and people with behavior disorders have abnormally low levels of a hormone system tied to blood pressure regulation and inflammation. In the cerebrospinal fluid of patients with first episode psychosis, she noticed abnormally low levels of the enzyme that makes the hormone angiotensin. To see if these results correlated to animals and could be studied in the lab, Hayes, who works in the laboratory of Akira Sawa, M.D., Ph.D., treated brain cells with angiotensin and inflammation activators in their mouse model for behavior disorders, then measured the output of proteins involved in inflammation. Compared to normal mice, the cells from the mouse with behavioral disorders released more inflammation protein when treated with low levels of angiotensin and less when treated with high levels. Next, she looked at gene expression levels of the angiotensin system components in the brain cells of the behavioral disorder mice. The gene expression levels for the receptor that detects angiotensin were abnormally low in a specific type of brain cell. Hayes says these specific cells in the behavior disorder mice seem to be less susceptible to angiotensin's immunosuppressive properties, because they have less receptor to detect angiotensin than the same brain cells in normal mice. Hayes and Sawa plan to investigate whether targeting angiotensin could control inflammation and perhaps treat psychosis.
Poster L2 795.02
Wed., 2 p.m., Walter E. Washington Convention Center, Halls A-C
Bindu Paul, Juan Sbodio, Risheng Xu, M. Scott Vandiver, Jin Cha, Adele Snowman, Solomon Snyder
Nutrient Deficiency Linked to Brain Wasting in Huntington's Disease
In a serendipitous finding, Johns Hopkins neuroscientist Bindu Paul, Ph.D., connected the manufacture of an essential amino acid to Huntington's disease, changing scientific understanding of the condition. Studying mice lacking the enzyme that makes cysteine, Paul, a researcher in the laboratory of Solomon Snyder, M.D., noticed the mice behaved like those used to study Huntington's disease: They remained still and clasped their paws together when dangled by their tails. Intrigued, Paul checked the amount of the cysteine-making enzyme in the Huntington's mice and found decreased levels in the disease-affected tissues. More experiments soon revealed that the mutant huntingtin protein, which causes the disease, gloms up the genetic machinery that generates the cysteine-making enzyme. Without the enzyme, much less cysteine is made. Paul fed the Huntington's mice diets rich in cysteine, and they regained normal behavior, swinging and biting when dangled by their tails. These unexpected findings have led to clinical trials to see if treatment with cysteine can relieve symptoms in people with Huntington's.
Poster S9 798.08
Wed., 4 p.m., Walter E. Washington Convention Center, Halls A-C
Mei Han, Rebeca Mejias-Estevez, Richard Huganir, Tao Wang
Autistic Mice Become Social with Drug Treatment
Researchers at Johns Hopkins improved the sociability of autistic mice by treating them with drugs that turn on specific receptors in the brain. Several years ago, Tao Wang, M.D., Ph.D., an associate professor of pediatrics, and Richard Huganir, Ph.D., a professor of neuroscience, found that mutations in genes that regulate a receptor in brain cells known as the AMPA receptor correlated with severe social defects in patients with autism. AMPA receptors detect the neurotransmitter glutamate and facilitate learning and memory. Wang's team tested drugs that affected the AMPA receptor in the autism mouse, an established laboratory mouse with known social interaction defects. They found that drugs that acted on the receptor in a similar way that glutamate does, initiating a whole series of internal cell messages that improved the social behaviors of the mice. Wang says that many studies implicate glutamate in autism, but this is the first time social behaviors in mice have been linked to AMPA receptors. Since the mice received only one dose of the drug in this study, the team next wants to test whether the treatment works long term. If so, drugs that affect AMPA receptors could potentially turn out to be effective treatments for social aversion in people with autism.
Nov. 15-19, 2014