Researchers at Massachusetts General Hospital (MGH) recently made a surprising discovery for males that are afflicted with autism spectrum disorder (ASD). Using cutting-edge imaging technology, the investigators found that the brains of young men with ASD have low levels of a protein that appears to play a role in inflammation and metabolism. Findings from the new study were published recently in Molecular Psychiatry through an article entitled “[11C]PBR28 MR–PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.”

Interestingly, the current study was the first to use a new generation of PET “tracers” to examine the brains of people with ASD.

ASD is a developmental disorder that emerges in early childhood and is characterized by difficulty communicating and interacting with others. While the cause is unknown, growing evidence has linked ASD to inflammation of brain tissue, or neuroinflammation. One sign of neuroinflammation is elevated levels of a substance called translocator protein (TSPO), which can be measured and located in the brain using positron-emission tomography (PET) and anatomical magnetic resonance imaging (MRI).

The MGH researchers scanned the brains of 15 young adult males (average age, 24) with ASD. The group included both high- and low-functioning subjects with varying degrees of intellectual abilities. For comparison, a team led by Nicole Zurcher, PhD, an investigator in MGH’s Athinoula A. Martinos Center for Biomedical Imaging and lead study author, scanned the brains of 18 healthy control subjects who were similar in age.

“We measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes,” the authors wrote. “Participants underwent scanning on a simultaneous magnetic resonance–positron emission tomography (MR–PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies.”

The investigators hypothesized that the scans would show increased levels, or expression, of TSPO in subjects who have ASD. “To our surprise, that’s not what we saw,” noted Zurcher. Instead, the scans showed that the brains of males with ASD had lower levels of TSPO than those of the healthy subjects.

In fact, the men with the most severe symptoms of ASD tended to have the lowest expression of TSPO. When the tests were repeated several months later, the pattern persisted. The brain regions found to have low expression of TSPO have previously been linked to ASD in earlier studies and are believed to govern social and cognitive capacities such as processing of emotions, interpreting facial expressions, empathy, and relating to others. “We know these brain regions are involved in autism,” said Zurcher.

To understand this unexpected finding, Zurcher noted that TSPO does more than serve as a marker of inflammation. “It has multiple complex roles,” she said, and some actually promote brain health. For example, adequate TSPO is necessary for the normal functioning of mitochondria, which are the “powerhouses” in cells that produce energy. Earlier research has linked malfunctioning mitochondria in brain cells to ASD.

The researchers plan to study brains from deceased donors with the goal of determining which brain cells in people with ASD might experience mitochondrial dysfunction, which she said may well be occurring alongside neuroinflammation and other mechanisms to cause ASD. “Our study has generated new hypotheses that now need to be investigated, but there’s more work to be done,” Zurcher concluded.

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