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Mouse Study: Common Fungus Can Lead to Brain Infection, Memory Problems

A new study finds that the common yeast Candida albicans, a type of fungus, can cross the blood-brain barrier and trigger an inflammatory response leading to the formation of granuloma-type structures and temporary mild memory impairments in mice. These granulomas share features with plaques found in Alzheimer’s disease.

Although Candida albicans is part of our natural microflora, it is an opportunistic pathogenic yeast that can cause infections, particularly in the gastrointestinal tract, mouth and vagina.

The findings, published in the journal Nature Communications, suggest the need for further research on the long-term neurological consequences of sustained C. albicans infection.

“An increasing number of clinical observations by us and other groups indicates that fungi are becoming a more common cause of upper airway allergic diseases such as asthma, as well as other conditions such as sepsis, a potentially life-threatening disease caused by the body’s response to an infection,” said corresponding author Dr. David B. Corry, professor of medicine-immunology, allergy and rheumatology and Fulbright Endowed Chair in Pathology at Baylor College of Medicine in Texas.

Importantly, Corry said, fungal infections causing airway allergic diseases and sepsis have been linked to an increased risk for dementia later.

“These observations led us to investigate the possibility that fungus might produce a brain infection and, if so, the consequences of having that kind of infection,” said Corry, who also is a member of the Dan L Duncan Comprehensive Cancer Center.

The research team developed a mouse model of a low-grade fungal infection with the common yeast C. albicans that would not cause severe disease, but might carry implications for brain function. They tested several doses and finally settled on one dose of 25,000 yeasts.

After injecting C. albicans into the blood stream of mice, the researchers were surprised to discover that the yeast was able to cross the blood-brain barrier, a robust protective mechanism the brain uses to keep out all kinds of large and small molecules, as well as a number of microorganisms that can potentially damage the brain.

“We thought that yeast would not enter the brain, but it does,” Corry said. “In the brain, the yeast triggered the activity of microglia, a resident type of immune cell. The cells became very active ‘eating and digesting’ the yeast. They also produced a number of molecules that mediated an inflammatory response leading to the capture of the yeasts inside a granule-type structure inside the brain. We called it fungus-induced glial granuloma, or FIGG.”

The researchers also tested memory skills in both yeast-infected and non-infected mice. They found that infected mice had impaired spatial memory, which reversed when the infection cleared.

Although the yeast infection resolved itself in about 10 days, the microglia remained active and the FIGGs persisted well past this point, out to at least day 21.

Importantly, as the FIGGs formed, amyloid precursor proteins accumulated within the periphery and amyloid beta molecules built up around yeast cells captured at the center of FIGGs. These amyloid molecules are typically found in plaques that are the hallmark of Alzheimer’s disease.

“These findings suggest that the role fungi play in human illness potentially goes well beyond allergic airway disease or sepsis,” Corry said.

“The results prompted us to consider the possibility that in some cases, fungi also could be involved in the development of chronic neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and multiple sclerosis. We are currently exploring this possibility.”

Source: Baylor College of Medicine



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