‘Transport error’ in the brain sheds light on Huntington’s

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Scientists have discovered a previously unknown error in the transport of glutamine in the brains of mice with Huntington’s disease. The finding may lead to the development of new treatments, the researchers believe.

There is currently no cure for Huntington’s, which causes personality alterations and loss of motor control. Now researchers have come one step closer to uncovering what actually happens in the brain of Huntington’s patients.

A new study in Cell Reports describes how an important exchange between astrocytes and neurons in the brain is disturbed during Huntington’s disease—more precisely, the glutamate-GABA-glutamine cycle. Researchers say this highlights the important role of astrocytes in the brain.

“Researchers used to believe that hereditary diseases—including Huntington’s disease—were primarily a result of problems in the neurons,” says first author Niels Henning Skotte, a postdoc at the University of Copenhagen.

“But here we show and confirm that the astrocytes also play a main role. Glutamine is produced in the astrocytes and transported to the neurons, where it is used to make neurotransmitters. They are central to the ability to send signals across the brain. If the transport of glutamine from the astrocytes is lost, the neurons stop functioning optimally.”

The researchers analyzed the protein alterations seen in the four regions of the brain—striatum, cortex, hippocampus, and diencephalon—in mice with advanced Huntington’s disease compared to healthy mice.

They found that the protein alterations affected the striatum more than the other regions of the brain, as in humans. They found a total of around 900 protein alterations. The researchers’ metabolic studies, which also showed a majority of disorders in the striatum, supported this.

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The researchers say the most study’s most important finding is the reduced exchange of glutamine between astrocytes and neurons. It’s an area with potential when it comes to future research into whether a normal release of glutamine from the astrocytes can potentially alleviate the symptoms of Huntington’s disease, they say.

“Even though Huntington’s disease is a genetic disease, our study shows a dysregulation of the proteins and the signaling pathways of these proteins,” says Michael Lund Nielsen, professor at the University of Copenhagen. “There is currently no cure for Huntington’s disease. But if we were able to find areas in which the effects of the disease may potentially be improved or reduced, it would be a big step in the right direction. This study may provide suggestions for focus areas of future research.”

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More research is necessary to clarify the role played by dysregulated glutamine transport in the development of Huntington’s disease. Data suggests, however, that the cycle is disturbed early in the course of the disease. If this proves correct, it may perhaps play an even greater role in the development of the disease, just as it may potentially increase the chances of alleviating the symptoms, the authors say.

The Novo Nordisk Foundation, the Independent Research Fund Denmark, Stadslæge Svend Ahrend Larsen and Grosserer Jon Johannesons Foundation, and Peter and Emma Thomsen’s Scholarship funded the work.

Source: University of Copenhagen