Autism, schizophrenia linked to same receptors in brain


Researchers from the Salk Institute for Biological Studies may have just found a mechanism in the brain that leads to autism or schizophrenia.

The research focused on a specific brain cell, the parvalbumin-positive interneurons, and a specific receptor on it known as mGluR5, two components of the brain tied to development and neural disorders.

Parvalbumin-positive (PV) interneurons are inhibitory brain cells, meaning they act on other neurons to keep them from firing. They’re thought to be critical in the brain, especially for certain kinds of memory and brain development in general—as when signaling from these cells was disrupted during development during a prior study, the brain’s networks didn’t form correctly.

Meanwhile, the receptor mGluR5 is found on PV neurons, as well as other cells in the brain. This receptor pairs with the neurotransmitter glutamate, allowing glutamate to interact with the cells. In non-PV neurons, the mGluR5 receptor has been found to be important in general cognition and in creating some types of oscillatory wave patterns in the brain. Further, previous studies linked mGluR5 to addiction disorders, anxiety, and Fragile X Syndrome.

Knowing how important the PV cells are for development, the Salk researchers wondered what effects mGluR5 may have on them. After partnering with a team from the Department of Psychiatry at the University of California, San Diego, they studied the effects of deleting the receptor from mice after initial brain formation was complete.

Behavioral deficits similar to schizophrenia

“We found that without this receptor in the parvalbumin [PV] cells, mice have many serious behavioral deficits,” said Terrence Sejnowski, head of Salk’s Computational Neurobiology Laboratory, in a press release. “And a lot of them really mimic closely what we see in schizophrenia.”

The mice with the knocked-out receptors in fact displayed a host of developmental problems, with some indicative of autism as well: obsessive, repetitive grooming behavior and anti-social tendencies, along with patterns of neural activity which resembled those seen in humans suffering from schizophrenia.

“This discovery implies that changes after birth, not just before birth, are affecting the way the network is set up,” says Margarita Behrens, corresponding author and Salk staff scientist.

Which would make sense, as some with autism spectrum disorder often go through what is known as a regression—meaning they appear to develop regularly for months or years, until they suddenly begin to lose previously acquired skills, like speech. Schizophrenia, meanwhile, usually begins to appear between the ages of 16 and 30. In both cases, it could be possible that genes, epigenetics, the environment, or any combination of the three suddenly causes the PV neurons to lose mGluR5 receptors, resulting in the development of the disorders.

Some good news

Sejnowski considers this to be good news, because these changes might be reversible.

“The cells are still alive, and if we can figure out how to go in and change some of these molecular switches, we might actually be able to put the cells back into healthy, functioning states,” he said.

Behrens, however, thought their results should be a warning to those attempting to modulate the effects of mGluR5 in attempts to resolve other disorders the receptor is linked to. “There are a lot of clinical trials ongoing looking at modulating mGluR5 for anxiety and Fragile X Syndrome,” she says. “But our results suggest that if you affect parvalbumin neurons, you might get behavioral changes you weren’t expecting.”

The full study can be found in Molecular Psychiatry.

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