Scientists identify the signature of an aging brain

Dry roasting could trigger peanut allergy

NOVEMBER 1, 2014 22:22

A scientist looks through a microscope (photo credit: INGIMAGE) — A scientist looks through a microscope

(photo credit: INGIMAGE)

How the brain ages is still largely an open question – in part because this most important organ is mostly insulated from direct contact with other systems in the body, including the blood and immune systems. In research that was recently published in the journal Science, Weizmann Institute researchers Prof. Michal Schwartz of the neurobiology department and Dr. Ido Amit of the immunology department found evidence of a unique “signature” that may be the “missing link” between cognitive decline and aging. The scientists believe that this discovery may lead in the future to treatments that can slow or reverse cognitive decline in older people.

Until a decade ago, scientific dogma maintained that the blood-brain barrier prevents the blood-borne immune cells from attacking and destroying brain tissue. Yet in a long series of studies, Schwartz’s group had shown that the immune system actually plays an important role both in healing the brain after injury and in maintaining the brain’s normal functioning. They have found that this brain-immune interaction occurs across a barrier that is actually a unique interface within the brain’s territory.

This interface, known as the choroid plexus, is found in each of the brain’s four ventricles, and it separates the blood from the cerebrospinal fluid. Schwartz: “The choroid plexus acts as a ‘remote control’ for the immune system to affect brain activity. Biochemical ‘danger’ signals released from the brain are sensed through this interface; in turn, blood-borne immune cells assist by communicating with the choroid plexus. This crosstalk is important for preserving cognitive abilities and promoting the generation of new brain cells.”

The discovery led Schwartz and her group to suggest that cognitive decline over the years may be connected not only to one’s chronological age but also to one’s immunological age – that is, changes in immune function over time might contribute to changes in brain function, not necessarily in step with how many birthdays one has had.

To test this theory, Schwartz and research students Kuti Baruch and Aleksandra Deczkowska teamed up with Amit and his research group in the immunology department.

The researchers used next-generation sequencing technology to map changes in gene expression in 11 different organs, including the choroid plexus, in both young and aged mice to identify and compare pathways involved in the aging process. That is how they identified a strikingly unique “signature of aging” that exists solely in the choroid plexus – not in the other organs.

They discovered that one of the main elements of this signature was interferon beta – a protein that the body normally produces to fight viral infection. This protein appears to have a negative effect on the brain: When the researchers injected an antibody that blocks interferon beta activity into the cerebrospinal fluid of the older mice, their cognitive abilities were restored, as was their ability to form new brain cells. The scientists were also able to identify this unique signature in elderly human brains. The scientists hope that this finding may, in the future, help prevent or reverse cognitive decline in old age, by finding ways to rejuvenate the immunological age of the brain.

DRY ROASTING COULD TRIGGER PEANUT ALLERGY

Dry roasted peanuts are more likely to trigger an allergy than raw peanuts, suggests an Oxford University study involving mice.

The researchers say that specific chemical changes caused by the high temperatures of the dry roasting process are recognized by the body’s immune system, “priming” the body to set off an allergic immune response the next time it encounters any peanuts.

The results might explain the difference in the number of people with peanut allergies in the Western world compared to populations in East Asia, the researchers say.

In the West, where roasted and dry-roasted peanuts are common, there are far more people with peanut allergies than in the East, where peanuts are more often eaten raw, boiled or fried. Numbers of people with other food allergies show no such difference.

In the study, published recently in the Journal of Allergy and Clinical Immunology, the researchers purified proteins from both dry-roasted and raw peanuts. They introduced the peanut proteins to mice in three different ways – injected under the skin, applied to broken skin and introduced directly into the stomach. The immune responses of the mice to further peanut extracts given later were measured.

The mice that had been initially exposed to dry roasted peanuts generated greatly increased immune responses to peanuts, compared to mice that had been exposed to raw peanut proteins. The types of immune responses seen are characteristic of allergic reactions.

Prof. Quentin Sattentau, who led the Oxford research, said: “This is the first time that a potential trigger for peanut allergy has been directly shown.” Previous studies have shown that roasting modifies peanut proteins leading to altered recognition by the immune system, but they did not show that roasted peanuts can trigger an allergic immune response.

Co-author Dr. Amin Moghaddam added: “Our results in mice suggest that dry roasted peanuts may be more likely to lead to peanut allergy than raw peanuts. The dry roasting causes a chemical modification of peanut proteins that appears to activate the immune system against future exposure to peanuts."

“Allergies in people are driven by multiple factors including family genetic background and exposure to environmental triggers. In the case of peanut allergy, we think we may have discovered an environmental trigger in the way that peanuts are processed by high-temperature roasting.”

Sattentau concluded: “We know that children in families with other allergies are more likely to develop peanut allergy. However our research is at an early stage, and we think that it would be premature to avoid roasted peanuts and their products until further work has been carried out to confirm this result. We think we have identified the chemical modifications involved in triggering an allergic response to peanuts and are currently exploring methods that are food industry-friendly to eliminate these groups.”