Research sheds light on histamine as a potential key player in depression

According to a new study of mice, inflammation of the body reduces the level of “comfortable molecules” and their ability to enhance antidepressants.

Research by researchers at Imperial College London and the University of South Carolina has increased evidence that inflammation and the associated release of histamine molecules affect serotonin, an important molecule involved in brain mood.

Reproduction in humans of findings identifying histamine as the “new molecule of interest” in depression could open new avenues for treating depression, the world’s most common mental health problem. There is sex.

Inflammation (a comprehensive term for an immune response) causes the release of histamine in the body. This increases blood flow to the affected area and floods it with immune cells. These effects help the body fight infections, but both long-term and acute inflammation are increasingly associated with depression.

Inflammation is associated with infections, but it can also be caused by many chronic diseases such as stress, allergic reactions, diabetes, obesity, cancer and neurodegenerative diseases.

Inflammation can play a major role in depression, and there is already strong evidence that patients with both depression and severe inflammation are most likely not responding to antidepressants.

Our work spotlights histamine as a potential key player in depression. Therefore, the interaction of this with the “comfortable molecule” serotonin may be an important new path in improving serotonin-based treatment of depression. “

Dr. Parastoo Hashemi, lead author, empire’s biotechnology department

Chemistry messenger

Serotonin, often referred to as the “comfortable molecule,” is an important target for drugs that address depression. Commonly prescribed selective serotonin reuptake inhibitors (SSRIs) block the reabsorption of serotonin in the brain, allowing serotonin to circulate longer and improve mood.

However, while SSRIs provide relief to many who take SSRIs, more and more are resisting their effects. Researchers believe that one reason for this may be chemical mediators, or specific interactions between neurotransmitters, including serotonin and histamine.

With this in mind, researchers set out to investigate the relationship between histamine, serotonin, and SSRIs.

They created serotonin-measuring microelectrodes and placed them in the hippocampus of the brain of living mice, an area known to regulate mood. Known as high-speed scan cyclic voltammetry (FSCV), it is biocompatible and only 5 micrometers wide, allowing real-time measurement of serotonin levels in the brain without harming the brain.

After placing microelectrodes, they injected half of the mice with lipopolysaccharide (LPS), an inflammatory toxin found in some bacteria, and half of the mice with saline as a control.

Serotonin levels in the brain decreased within minutes of LPS injection, but remained the same in control mice. This shows how quickly the inflammatory response in the body is transformed into the brain and affects serotonin. LPS could not directly cause this decline because it could not cross the blood-brain barrier.

In further investigation, they found that histamine in the brain was triggered by an inflammatory response and attached directly to the inhibitory receptors of serotonin neurons to directly inhibit the release of serotonin. These inhibitory receptors are also present in human serotonin neurons, so this effect may be transmitted to people.

To counter this, researchers administered SSRIs to mice, but failed to raise serotonin levels higher than control mice. They argued that this was because SSRIs directly increased the amount of histamine in the brain, counteracting its serotonin-enhancing effect.

Researchers then administered histamine-reducing drugs with SSRIs to counteract the inhibitory effects of histamine and saw serotonin levels return to control levels. This seems to support the theory that histamine directly attenuates serotonin release in the mouse brain. These histamine-reducing drugs are different from the antihistamines taken for allergies that cause a systemic decrease in histamine and block the effects of histamine on neurons.

New molecule of interest

Researchers say that if their work is translated into humans, it could ultimately help diagnose depression by measuring chemicals such as serotonin and histamine in the human brain. Stated.

They also say that this discovery opens new avenues for exploring histamine as a causative agent of depression, including the possibility of developing new drugs that reduce histamine in the brain.

Since the work was done on animals, more research is needed to find out if the concept is transformed into humans. However, it is currently not possible to make similar measurements in the human brain using microelectrodes, so researchers are now looking at other organs that use serotonin and histamine, such as the intestine, to make the brain. I’m looking at other ways to take a snapshot of.

Inflammatory pain can also alter neurotransmitter levels, but previous studies have shown that these changes last for minutes in similar models, but this study showed them. The decrease in serotonin lasts much longer, excluding pain as the reason for the decrease in serotonin.

Dr. Hashemi added: “Inflammation is very complex because it is a systemic reaction. Depression is just as complex, and the chemicals involved are affected in a myriad of ways by both genetic and environmental factors. Therefore, depression To get a complete picture of the roles of both histamine and serotonin in disease, we need to look at more complex models of depressive behavior in both mice and humans. “