Understand the brain’s response to chronic stress!

Scientists at Augusta University Georgia School of Medicine looked at the hypothalamus, key to functions such as hormone release and regulation of hunger, thirst, mood, sex drive and sleep. , at a subpopulation of neurons called proopiomelanocortin, or POMC, neurons, in response to 10 days of chronic, unpredictable stress.

Chronic unpredictable stress is widely used to study the effects of stress exposure in animal models and in this case includes things like limited, prolonged wet beds in inclined cages and social isolation.


Potential treatment for stress-induced behavioral disorders

They found stressors increase spontaneous firing of these POMC neurons in male and female rats, corresponding author Xin-Yun Lu, MD, PhD, chair of the MCG Department of Neuroscience and Regenerative Medicine and Distinguished Scholar of the Georgia Research Alliance in Translational Neuroscience.

When they directly activated the neurons, rather than letting stress increase their activity, it also resulted in an inability to experience pleasure, known as anhedonia, and behavioral despair. , is essentially depression.

In humans, signs of anhedonia can include no longer interacting with good friends and loss of libido. In rats, their usual love of sugar water dwindled, and male rats, which often liked to smell female urine during heat, also lost some interest.

In contrast, when the MCG scientists inhibited neuronal activity, it reduced the types of stress-induced behavioral changes in both sexes.

The results showed that POMC neurons were “just needed” to increase their susceptibility to stress, and that their increased activity was responsible for behavioral changes such as depression. Stress markedly reduces inhibitory inputs to POMC neurons, says Lu.

POMC neurons are located in the arcuate nucleus, or ARC, of ​​the hypothalamus, an arcuate brain region has been thought to be important for how chronic stress affects behavior.

Lu and her team reported in the journal Molecular Psychiatry in early 2021, occupying the same region as another subpopulation of neurons, called AgRP neurons, that are critical for resiliency. response to stress and chronic depression.

In the face of chronic stress, Lu’s lab reported that AgRP activation decreases when behavioral changes such as anhedonia occur, and when they stimulate those neurons the behavior decreases. . Her team also wanted to know how chronic stress affects POMC neurons.

AgRP neurons, better known for their role in helping us find food when we’re hungry, is known to have a yin-positive relationship with POMC neurons: For example, when AgRP activation increases, POMC activation decreases.

“If you stimulate AgRP neurons, it can trigger an immediate and powerful energizing process,” says Lu. Lack of food also increases the activity of these neurons. It is also known that when stimulated by hunger signals, AgRP neurons send messages directly to POMC neurons to release the brake when eating.

Exploring the intrinsic mechanism of POMC . neurons

Their studies found that chronic stress disrupts the yin and yang balance between these two neuronal populations. Although the prediction of AgRP to POMC neurons is important for their firing activity, the intrinsic mechanism is probably the main mechanism underlying hyperactivity, Lu said. of POMC neurons due to chronic stress.

Intrinsic mechanisms may include potassium channels in POMC neurons that are known to respond to a variety of signals and, when open, lead to potassium efflux of the cell, reducing cellular excitability. nerve.

While the potential role of these potassium channels in POMC neurons in stress response needs study, The scientists suspect stress also affects potassium channels, and that opening those channels could be a possible targeted treatment to restrain POMC neurons from firing violently.

Overactivity of nerve cells is also known to cause seizures and there are anticonvulsant drugs that are given to open potassium channels and reduce that excessive firing. There’s even some early clinical evidence that these drugs can also help treat depression and anhedonia, and what the Lu lab is finding may help explain why.

Lu is yet to learn, but she wants to further explore the role of these channels to better understand how stress affects them in POMC neurons and how best to target the channels if detected. Their work further shows that they play a key role in interesting POMC neurons.

According to the American Psychological Association, chronic stress affects all body systems. Even muscles stretch to prevent injury and pain. Stress can make breathing difficult, especially in people with pre-existing breathing problems such as asthma.

In the long run, it can increase the risk of high blood pressure, heart attack and stroke, and even alter the good bacteria in our gut that help us digest food.

Source: Eurekalert


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