Agouti-related peptide (AgRP) neurons are a small group of cells that control hunger and body temperature. They also send signals to higher brain areas. When AgRP neurons don’t work right, the ventral tegmental area (VTA) gets more active. It releases more dopamine and has bad effects on the frontal cortex.
Summary: Treating mental health problems like major depression is hard. In a new study, researchers propose a new focus. Instead of higher brain centers, we should look at more primitive brain areas like the brain stem. That is because groups of nerve cells in the brain stem can significantly affect higher brain functions like thinking, mood and more.
Also, the brain stem is not walled off by the blood-brain barrier. The study also shows that treatments given during puberty are more likely to have a significant effect.
The brain makes us who we are. So if anything goes wrong with the brain, the result may be devastating. Even small brain changes may cause significant disability. They may lead to severe mental illness like schizophrenia or major depression.
But the brain is very complex, so it is hard to understand how it grows and works. Science knows a bit about what each part of the brain does. But it knows little about how brain parts talk to each other and work together. For example, science knows the prefrontal cortex (front part of the brain) plays a key role in thinking, decisions and memory. The brain stem, deep inside, runs most body functions we need to stay alive. So the brain stem is called the primitive brain. All mammals have one. It runs basic but vital functions like hunger, body temperature, breathing and so on. But the brain stem does not take part in complex decisions, thinking, memory and the like.
Nerve cells in the brain stem run vital body functions. But they may also shape higher brain functions like thinking, intelligence and memory, since thinking also helps us survive. So in the new study, researchers focused on a group of nerve cells in the brain stem or hypothalamus called agouti-related peptide (AgRP). These cells play a key role in eating and in body temperature control. The group of AgRP cells is small, but its effect on health is huge. After all, they make sure we eat enough. It also makes sense that they might send signals to higher brain areas. After all, higher brain areas are in charge of finding food and keeping us safe and alive.
In the new study, researchers found some new pathways. For example, when AgRP cells don’t work right, the midbrain, or ventral tegmental area, gets more active. It releases more dopamine, which has some bad effects on the frontal cortex. Researchers say this makes sense. Hunger and eating have a significant effect on how animals behave. When you are hungry, you go looking for food. When you are not hungry, the brain acts differently. It also means that tuning AgRP cells can help tune the higher brain centers. They found that one drug, called clozapine, could block dopamine.
But they found the drug worked better at tuning these pathways during puberty, while the brain was still growing. Researchers say this also shows that dieting or overeating during puberty, while the brain is growing, can have a lasting effect on higher brain functions. It also means mental health problems must be spotted earlier, since they can be treated better during this time. This fits with the fact that many mental health problems get worse from puberty on. So puberty is also the best time to manage these problems.
Researchers say there is another upside. The brain stem sits outside the blood-brain barrier, and AgRP cells are in the brain stem. So many drugs that cannot cross the blood-brain barrier can still reach cells in the brain stem and help manage mental health problems. These brain cells are also easier to reach with treatment. So researchers concluded that a better way to treat mental health problems or brain disorders may be drugs that act on more primitive brain areas. Keep in mind that higher brain areas are always talking with these primitive areas.
Frequently asked questions
What are AgRP neurons?
AgRP stands for agouti-related peptide. AgRP neurons are a small population of brain cells that control feeding and body temperature. Their job is to make sure the body takes in enough food, so their impact on health and well-being is large for such a small group of cells. They also send signals up to the higher brain areas that handle finding food and staying safe.
What happens in the brain when AgRP neurons are impaired?
When AgRP neurons stop working right, the ventral tegmental area in the midbrain gets more active and releases more dopamine. That extra dopamine has bad effects on the frontal cortex, the part of the brain that handles thinking, decisions and memory. In other words, a hunger circuit can change how the thinking brain works.
Does hunger change how the brain behaves?
Yes. Hunger and eating have a strong effect on behavior. When you are hungry, the brain pushes you to go looking for food. When you are not hungry, it acts differently. AgRP neurons sit at the center of that drive. So researchers say that changing how these cells work can also change how the higher brain centers work.
Can dieting or overeating during puberty affect brain development?
The researchers say it can. Their findings suggest that dieting or overeating during puberty, while the brain is still growing, can have a lasting effect on higher brain functions. A drug they tested worked better at tuning these brain pathways during puberty. That fits with the fact that many mental health problems get worse from puberty on.
Could this research change how depression is treated?
It points in a new direction. Instead of focusing only on higher brain centers, the researchers propose treating mental health problems such as major depression through more primitive brain areas. Those areas control hunger and other basic functions. In the study, the drug clozapine blocked dopamine, and it worked best during puberty. That argues for spotting these problems earlier.
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The same appetite wiring is part of why weight change is hard to keep up without medical support for weight management.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
