Chronic stress can affect our behavior, causing problems such as depression, loss of interest in things that previously brought us pleasure, and even PTSD. Now scientists have evidence that a group of neurons in the bow-shaped part of the brain becomes hyperactive after prolonged exposure to stress. When these POMC neurons become overactive, these kinds of behavioral problems arise, and when the scientists reduce their activity, it reduces the behavior.
The report was published in the journal Molecular Psychiatry. Scientists at the Medical College of Georgia at Augusta University looked in the hypothalamus, a population of neurons called proopiomelanocortin, or POMC, neurons that are key to releasing hormones and controlling functions such as hunger, thirst, mood, sex drive and sleep. 10-day-old, unpredictable stress response.
Chronic unpredictable stress is widely used to study the effects of stress exposure in animal models, and in this case it includes things like restraint, wet bedding for long periods of time in a tilted cage, and social isolation. They found that stress increased the spontaneous firing of these POMC neurons in male and female mice, says corresponding author Shin-Yoon Lu, MD, PhD, MCG Department of Neuroscience and Regenerative Medicine and Georgia Research Alliance Distinguished Scholar in Translational Medicine. Neuroscience.
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When they directly activated the neurons, instead of causing stress to increase their firing, it resulted in an inability to feel pleasure, called anhedonia, and behavioral despondency, which is essentially depression. In humans, indicators of anhedonia may include no longer interacting with good friends and decreased libido.
In rats, their usual fondness for sugar water wanes, and male rats, who usually prefer to smell the urine of females in heat, lose some of their interest as well. In contrast, when the MCG scientists inhibited the firing of neurons, it reduced these types of stress-induced behavioral changes in both sexes.
The results indicate that POMC neurons are “both necessary and sufficient” to increase sensitivity to stress, and that their increased firing is a driver of the resulting behavioral changes such as depression. Lu says that stress reduces the inhibitory input on POMC neurons. POMC neurons are in the arcuate nucleus, or ARC, of the hypothalamus, a bow-shaped brain region already thought to be important in how chronic stress affects behavior.
Occupying the same area is another population of neurons, called AgRP neurons, which are important for resilience to chronic stress and depression, Lu and his team report in Molecular Psychiatry in early 2021.
When exposed to chronic stress, Lu’s lab reported that reduced AgRP activation caused behavioral changes such as anhedonia and reduced behavior when they stimulated those neurons. His team also wanted to know what chronic stress does to POMC neurons. AgRP neurons, better known for their role in searching for food when we are hungry, are known to have a yin-yang relationship with POMC neurons: when AgRP activation goes up, for example, POMC activation drops below.
“If you stimulate AGRP neurons it can trigger immediate, stronger eating,” Lu says. Lack of food also increases the firing of these neurons. It is also known that when stimulated by hunger signals, AGRP neurons send direct messages to POMC neurons to release the brake on food. Their study found that chronic stress disrupts the yin-yang balance between these two neuronal populations.
Although the projection of AgRP to POMC neurons is important for their firing activity, intrinsic mechanisms are likely the dominant mechanism underlying the hyperactivity of POMC neurons from chronic stress, Lu says. The intrinsic mechanism may involve potassium channels in POMC neurons that are known to respond to a range of different signals, and when open, allow potassium to flow out of the cell, reducing neuronal excitability.
While the potential role of these potassium channels in POMC neurons in response to stress needs to be studied, scientists suspect that stress also affects potassium channels and that opening those channels could be a potentially targeted treatment to stop the wildly firing of POMC neurons. It is possible
Excessive activity of neurons is also known to cause seizures and anticonvulsants are given to open potassium channels and reduce that excessive firing. There is even some preliminary clinical evidence that these drugs may also help treat depression and anhedonia, and what the Lu lab is discovering may help explain why.
Lu hasn’t seen one yet, but she wants to explore the role of these channels in POMC neurons to better understand how stress affects them and how to target the channels if her findings suggest they are excitable. POMCs play an important role in neurons. , According to the American Psychological Association, chronic stress affects all body systems.
Muscles also become tense to avoid injury and pain. Stress can cause shortness of breath, especially in people who already have respiratory problems like asthma. In the long run, it can increase the risk of high blood pressure, heart attack and stroke, even altering the good bacteria in our gut that help us digest food. The research was funded by the National Institutes of Health.