Mole-rats’ failure to social distance offers clue for treating some neurological disorders

NEW YORK, April 30, 2020 (print edition) — A new study from researchers at The Graduate Center, CUNY; College of Staten Island; and The University of Helsinki provides insight into what may be occurring in the brains of people with certain neurological conditions, including autism spectrum disorder, epilepsy, and schizophrenia. The work could point toward useful therapies in treating these disorders.

The newly published findings in

Current Biology

explain why the African naked mole-rat, one of only two mammals to lead eusocial lives, never leave their colony to start new families and pile on top of each other in large groups to sleep inside their nest. Researchers found that these animals have a mutation of the gene for the KCC2 protein, which normally helps inhibit neurons. The variant, called R952H, causes the naked mole-rat to have a harder time suppressing brain activity, so that breathing in uninhibited levels of oxygen when the animals are inactive causes their brains to race and leads to a possible panic response and seizures. But the higher levels of carbon dioxide in their tightly packed nests inhibits brain activity, preventing this response. The researchers confirmed this connection by finding a similar genetic variant in the Damaraland mole-rat, the only other eusocial mammal.

Human brains also require a certain amount of inhibition to operate properly, and KCC2 protein function is developmentally regulated in humans and most other mammals. The mutation of this protein can be responsible for a glitch in brain activity suppression. Interestingly, the R952H variant thought to be responsible for this glitch in mole -rats has been reported in people with autism spectrum disorders, schizophrenia, and epilepsy.

“The link to humans with the R952H is what drives a lot of our questions,” said Daniel McCloskey, a psychology professor at The Graduate Center and College of Staten Island. “This has opened our eyes to the idea that some people around us may be more sensitive to the air we breathe and how we breathe it. Maybe there is a fix that can help these people feel more comfortable.”

The study proposes that the naked mole-rat could be used as a model to find treatments for people with this genetic difference. Conjunction therapy, in which carbon dioxide or drugs that lower neuron pH is added to an existing treatment regimen, may provide some benefits to individuals with certain neurological disorders and the R952H variant, the study authors noted.

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This study was supported through funding from the National Science Foundation, The Academy of Finland, and The Jane and Aatos Erkko Foundation.

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