Researchers Create “Mini-Brains” to Study Neurologic Diseases
Researchers at the Johns Hopkins Bloomberg School of Public Health in Baltimore have developed “mini-brains” made up of many of the neurons and cells of the human brain. The mini-brains have some of the human brain’s functionality and can be replicated on a large scale. Each mini-brain is a ball of brain cells that grow and form brainlike structures on their own over the course of eight weeks.
The mini-brains could change how new drugs are tested for effectiveness and safety by replacing the animals used for neurologic research in the United States. Performing research using these three-dimensional mini-brains should be superior to studying mice and rats because they are derived from human cells instead of rodent cells, the researchers said.
“Ninety-five percent of drugs that look promising when tested in animal models fail once they are tested in humans at great expense of time and money,” said Thomas Hartung, MD, PhD, the Doerenkamp-Zbinden Professor and Chair for Evidence-Based Toxicology at the Bloomberg School. “While rodent models have been useful, we are not 150-pound rats. And even though we are not balls of cells either, you can often get much better information from these balls of cells than from rodents. We believe that the future of brain research will include less reliance on animals, more reliance on human, cell-based models.”
Dr. Hartung and his colleagues created the brains using induced pluripotent stem cells (iPSCs) that were stimulated to grow into brain cells. Cells from the skin of several healthy adults were used to create the mini-brains, and Dr. Hartung said that cells from people with certain genetic traits or certain diseases can be used to create brains to study various types of pharmaceuticals. The brains can be used to study Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Projects to study viral infections, trauma, and stroke have been started.
The mini-brains are 350 mm in diameter, and hundreds or thousands of exact copies can be produced in each batch. One hundred of the mini-brains can grow easily in the same petri dish in the laboratory. After two months of cultivation, the mini-brains developed four types of neurons and two types of support cells: astrocytes and oligodendrocytes.
The researchers watched the myelin developing and saw it begin to sheath the axons. The brains also showed spontaneous electrophysiologic activity that could be recorded with electrodes, similar to an EEG. To test them, the researchers placed a mini-brain on an array of electrodes and listened to the spontaneous electrical communication of the neurons as test drugs were added.
“We don’t have the first brain model, nor are we claiming to have the best one,” said Dr. Hartung “But this is the most standardized one. And when testing drugs, it is imperative that the cells being studied be as similar as possible to ensure the most comparable and accurate results.”
Dr. Hartung is applying for a patent for the mini-brains and is also developing a commercial entity called ORGANOME to produce them. His goal is to begin production in 2016. The mini-brains are easily reproducible, Dr. Hartung said, and he hopes to see them used by scientists in as many laboratories as possible. “Only when we can have brain models like this in any laboratory at any time will we be able to replace animal testing on a large scale,” he said.
Loss of Slow-Wave Sleep Increases Risk of Diabetes
How much slow-wave sleep a teenage boy gets may predict whether he is at risk for insulin resistance and other health issues, according to Jordan Gaines, a doctoral candidate in neuroscience at Penn State College of Medicine in Hershey, Pennsylvania.
Boys who have a greater decline in slow-wave sleep as adolescents have a significantly higher chance of developing insulin resistance than those who more closely maintain their slow-wave sleep as they get older. The former are also at greater risk for developing type 2 diabetes, increased visceral fat, and impaired attention.
Slow-wave sleep is involved in memory consolidation and recovery after sleep deprivation, and is also associated with reduced cortisol and inflammation. While prior research has shown that slow-wave sleep declines with age, little research has examined possible physical or neurocognitive consequences of the loss of slow-wave sleep, said Ms. Gaines.
“On a night following sleep deprivation, we’ll have significantly more slow-wave sleep to compensate for the loss,” she added. “We also know that we lose slow-wave sleep most rapidly during early adolescence. Given the restorative role of slow-wave sleep, we weren’t surprised to find that metabolic and cognitive processes were affected during this developmental period.”