StemCell Therapy

People withanorexia nervosahave a distorted body image and severely restrict their food to the point of emaciation and sometimes death. It's long been treated as a psychological disorder, but that approach has had limited results; the condition has one of the highest mortality rates among psychiatric conditions. But recently, neuroscience researchers at the UC San Diego School of Medicine who study the genetic underpinnings of psychiatric disorders have identified a possible gene that appears to contribute to the onset of the disease, giving scientists a new tool in the effort to understand the molecular and cellular mechanisms of the illness.

The study, published in Translational Psychiatry, was led by UC San Diego's Alysson Muotri, a professor at theSchool of Medicines departments of pediatrics and cellular and molecular medicine and associate co-director of the UCSD Stem Cell Program. His team took skin cells known as fibroblasts from seven young women with anorexia nervosa who were receiving treatment at UCSDs outpatient Eating Disorders Treatment and Research Center, as well as from four healthy young women (the study's controls). Then the team initiated the cells to become induced pluripotent stem cells (iPSCs).

The technique, which won researcher Shinya Yamanaka the Nobel Prize in 2012, takes any nonreproductive cell in the body and reprograms it by activating genes on those cells. You can push the cells back into the development stage by capturing the entire genome in a pluripotent stem cell state, similar to embryonic stem cells, Muotri tells mental_floss. Like natural stem cells, iPSCs have the unique ability to develop into many different types of cells.

Once the fibroblasts were induced into stem cells, the team differentiated the stem cells to become neurons. This is the most effective way to study the genetics of any disorder without doing an invasive brain biopsy, according to Muotri. Also, studying animal brains for this kind of disorder wouldnt have been as effective. At the genetic level as well as the neural network, our brains are very different from any other animal. We dont see chimpanzees, for example, with anorexia nervosa. These are human-specific disorders, he says.

Once the iPSCs had become neurons, they began to form neural networks and communicate with one another in the dish similar to the way neurons work inside the brain. Basically what we have is an avatar of the patients brain in the lab, Muotri says.

His team then used genetic analysis processes known as whole transcriptome pathway analysis to identify which genes were activated, and which might be associated with the anorexia nervosa disorder specifically.

They found unusual activity in the neurons from the patients with anorexia nervosa, helping them identify a gene known as TACR1, which uses a neurotransmitter pathway called the tachykinin pathway. The pathway has been associated with other psychiatric conditions such as anxiety disorders, but more pertinent to their study, says Mutori, is that tachykinin works on the communication between the brain and the gut, so it seems relevant for an eating disorderbut nobody has really explored that. Prior research on the tachykinin system has shown that it is responsible for the sensation of fat. So if there are misregulations in the fat system, it will inform your brain that your body has a lot of fat.

Indeed, they found that the AN-derived neurons had a greater number of tachykinin receptors on them than the healthy control neurons. This means they can receive more information from this neurotransmitter system than a normal neuron would, Muotri explains. We think this is at least partially one of the mechanisms that explains why [those with anorexia] have the wrong sensation that they have enough fat.

In addition, among the misregulated genes, connective tissue growth factor (CTGF), which is crucial for normal ovarian follicle development and ovulation, was decreased in the AN samples. They speculate that this result may explain why many female anorexia patients stop menstruating.

Muotrinext wants to understand what he calls the downstream effect of those neurons with too many TACR1 receptors. In other words, how does it affect the neurons at a molecular level, and what information do those neurons receive from the gut? This link between the brain and the gut is unclear, so we want to follow up on that, he says.

He also wants to look into thepotential to design a drug that could compensate for the large amount of TACR1 receptors, and the over-regulation of that receptor in the brainwhich would be a huge development for the notoriously difficult-to-treat disease.

While Muotri is excited about new avenues of research that can follow from this work, he doesn't see it as a panacea for the disease, but a way to begin to understand it more fully. He says, Its a good start, but arguably you have to understand what are the other environmental factors that contribute.

Read more:
Scientists Say They've Identified a Gene Linked to Anorexia - Mental Floss

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