How chronic stress impacts behaviour, causes depression found

Washington: Chronic stress can impact behaviour, leading to problems like depression, reduced interest in things that previously brought us pleasure, even post-traumatic stress disorder (PTSD), according to a new study conducted in mice.

Scientists have evidence that a group of neurons in a bow-shaped portion of the brain, the hypothalamus, become hyperactive after chronic exposure to stress. When these proopiomelanocortin or POMC, neurons became super active, these sort of behavioral problems resulted and when scientists reduced their activity, the behaviours reduced, the study said.

According to the study, scientists at the Medical College of Georgia (MCG), Augusta University, US, looked in the hypothalamus, key to functions like releasing hormones and regulating hunger, thirst, mood, sex drive and sleep, at a population of POMC neurons in response to 10 days of chronic, unpredictable stress.

Chronic unpredictable stress is widely used to study the impact of stress exposure in animal models, and in this case, that included things like restraint, prolonged wet bedding in a tilted cage and social isolation, the study said.

The scientists found the stressors increased spontaneous firing of these POMC neurons in male and female mice, said corresponding author Xin-Yun Lu.

The scientists have reported their findings in the journal Molecular Psychiatry.

When they directly activated the neurons, rather than letting stress increase their firing, it also resulted in the apparent inability to feel pleasure, called anhedonia, and behavioral despair, which is essentially depression, the study said.

In humans, indicators of anhedonia might include no longer interacting with good friends and a loss of libido. In mice, their usual love for sugar water wanes, and male mice, who normally like to sniff the urine of females when they are in heat, lose some of their interest as well, the study said.

Conversely, when the MCG scientists inhibited the neurons' firing, it reduced these types of stress-induced behavioral changes in both sexes, the study said.

The results indicate POMC neurons are "both necessary and sufficient" to increase susceptibility to stress, and their increased firing is a driver of resulting behavioral changes like depression. In fact, stress overtly decreased inhibitory inputs onto POMC neurons, said Lu.

The POMC neurons are located in the arcuate nucleus, or ARC, of the hypothalamus, already thought to be important to how chronic stress affects behaviour.

Occupying the same region is another population of neurons, called AgRP neurons, which are important for resilience to chronic stress and depression, Lu and her team reported in Molecular Psychiatry in early 2021, the study said.

In the face of chronic stress, Lu and her team reported that AgRP activation goes down as behavioral changes like anhedonia occur, and that when they stimulated those neurons the behaviours diminished.

Her team also wanted to know what chronic stress does to the POMC neurons, the study said.

AgRP neurons, better known for their role in us seeking 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 goes down.

"If you stimulate AgRP neurons it can trigger immediate, robust feeding," Lu says.

Food deprivation also increases the firing of these neurons. It is also known that when excited by hunger signals, AgRP neurons send direct messages to the POMC neurons to release the brake on feeding.

The scientists' studies found that chronic stress disrupts the yin-yang balance between these two neuronal populations.

Although AgRP's projection to POMC neurons is clearly important for their firing activity, the intrinsic mechanism is probably the major mechanism underlying hyperactivity of POMC neurons by chronic stress, Lu said.

The research was funded by the National Institutes of Health, US.