How uncontrolled inflammation leads to brain cell loss

(A)s we get older, a vicious cycle of poorly regulated inflammatory responses leads to the loss of brain cells.

The researchers say that the immune response in the brain is mounted via microglial cells, a type of specialized immune cell found in the central nervous system, which includes the brain and the spinal chord.

Microglia work by responding to bacteria and clearing out malfunctioning nerve cells. At the same time, they send signals to recruit other types of immune cells and trigger inflammation when needed.

However, if unregulated, an inflammatory reaction in the brain can misguidedly attack and damage healthy brain tissue.

“We know that so-called endocannabinoids play an important role in this,” explains study co-author Dr. Andras Bilkei-Gorzo. “[Endocannabinoids],” he goes on, “are messenger substances produced by the body that act as a kind of brake signal: [t]hey prevent the inflammatory activity of the glial cells.”

These messenger substances act by binding to certain receptors, one of which is CB1. A second one is cannabinoid receptor type 2 (CB2).

Dr. Bilkei-Gorzo says, “The inflammatory activity of the microglial cells was permanently increased in these animals.” However, in mice with fully functioning CB1 receptors, inflammation was regulated as usual.

“Based on our results,” he says, “we assume that CB1 receptors on neurons control the activity of microglial cells.”

This has led the researchers to theorize that microglial cells do not communicate with other nerve cells directly. Instead, the scientists believe, microglial cells release endocannabinoids, and these bind to the CB1 receptors found in nearby neurons.

These neurons might be able to communicate with other nerve cells, and the immune response is thus indirectly regulated.

However, Dr. Bilkei-Gorzo and his team explain that with age, the production of endocannabinoids progressively decreases, leading to the improper regulation of immune responses and potentially to chronic inflammation.

“Since the neuronal CB1 receptors are no longer sufficiently activated, the glial cells are almost constantly in inflammatory mode,” says Dr. Bilkei-Gorzo.

“More regulatory neurons die as a result, so the immune response is less regulated and may become free-running,” he adds.

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