Researchers from the Weizmann Institute have discovered a unique “signature” in the brains of both elderly humans and mice that could be a missing link between cognitive decline and aging. The signature, which negatively affects brain function, could represent a novel therapeutic target for slowing or ameliorating the decline in cognitive abilities that are commonly associated with aging. The work has been published in Science.
As the control and information center of our bodies, the brain needs to be protected from potential dangers. One of the main ways that this is achieved is by shielding it with a highly selective barrier that separates it from circulating blood. This blood-brain barrier normally also keeps immune cells out which led scientists to believe not only that these two systems represented isolated entities, but also that immune cells are detrimental to the brain. However, scientists realized that it was unlikely that the brain is unable to recruit this system that is essential for our body’s maintenance and repair. Furthermore, scientists are now starting to demonstrate its role in brain health, function and aging.
A few years back, the leader of the current study, Professor Michal Schwartz, and her team demonstrated that the brain and the immune system can interact across a unique interface called the choroid plexus. This barrier is found in each one of the brain’s four ventricles and is designed to separate the blood from the cerebrospinal fluid.
“The choroid plexus acts as a ‘remote control’ for the immune system to affect brain activity,” Schwartz said in a news release. “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 cross-talk is important for preserving cognitive abilities and promising the generating of new cells.”
This discovery hinted that the well-established gradual deterioration of immune function that occurs as we age could also be associated with, or contribute to, cognitive decline. To find out if this is true, Schwartz and her team looked for genetic changes in mice of different ages. Specifically, they used sequencing to compare changes in gene expression in 11 different organs, including the choroid plexus, in young and elderly mice.
They found a unique gene expression profile, or signature, that existed solely in the choroid plexus of aged mice. Furthermore, they discovered that this signature was dependent on a type of immune system protein molecule called interferon-beta (IFN-β) that is normally produced to fight off viruses, but seems to have a negative effect on the brain. When the researchers blocked this molecule with an antibody that was injected directly into the cerebrospinal fluid of aged mice, they found that some cognitive function was restored. Furthermore, new brain cell growth was stimulated in the hippocampus, which is the region critical to learning and memory.
The team also discovered this signature in the brains of elderly humans, suggesting it is not unique to mice. This suggests that one day, with further research, scientists may be able to target this molecule to slow or even reverse cognitive decline in aging humans.