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May 19, 2017
Digest

Human Forebrain Circuits Under Construction in a Dish

NIH-funded neuroscientists have created a 3-D window into the human brain’s budding executive hub assembling itself during a critical period in prenatal development. What’s more, they used it to discover and experimentally correct—in a petri dish—defective cell migration caused by an autism-related disorder.

Dr. Sergiu Pasca, an NIMH grantee at Stanford University, and colleagues reported on experiments with forebrain spheroids Apr. 26 online in the journal Nature.

The study advances a fast-developing “disease-in-a-dish” technology, in which cultured neurons derived from an individual’s readily accessible skin cells connect with each other to form 3-D brain organoids or “spheroids.”

Although tiny, these replicate rudimentary circuitry that can reveal a person’s brain’s unique secrets—even from when it was still under construction.

During mid-to-late gestation, neurons migrate from deep brain structures to their appointed places and organize themselves into the key working tissue of what will become the human cortex, the outer layer of the brain and seat of higher-order mental functions. This building process is complex and especially vulnerable to genetic and environmental insults that can set the stage for autism, schizophrenia and other neurodevelopmental brain disorders.

Discovery in Mice Could Lead to New Meds Against Obesity

A team of scientists led by NIH researchers has identified an enzyme that could help in the continuous battle against mid-life obesity and fitness loss. The discovery in mice could upend current notions about why people gain weight as they age and could one day lead to more effective weight-loss medications.

“Our society attributes the weight gain and lack of exercise at mid-life (approximately 30-60 years) primarily to poor lifestyle choices and lack of will power, but this study shows that there is a genetic program driven by an overactive enzyme that promotes weight gain and loss of exercise capacity at mid-life,” said lead study author Dr. Jay H. Chung, head of the NHLBI Laboratory of Obesity and Aging Research.

Chung and his team used mice to test the potentially key role this enzyme plays in obesity and exercise capacity. They administered an inhibitor that blocked the enzyme in one group being fed high-fat foods, but withheld it in another. The result was a 40 percent decrease in weight gain in the group that received the inhibitor.

The study, the first to link the increased activity of this enzyme to aging and obesity, appeared in the May 2 issue of Cell Metabolism. Its findings could have ramifications for several chronic illnesses.

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