Neurons Responsible For Appetite May Treat Depression

Group of neurons called AgRP neurons responsible for appetite, may also play a role in depression that outcome from unpredictable, chronic stress.

Group of neurons that are responsible for appetite may also play a role in depression that outcome from unpredictable, chronic stress as per a study at Medical College of Georgia, published in the journal Molecular Psychiatry.

The hypothalamus – part of the brain involved in regulating various body functions especially the release of hormones, consists of AgRP (agouti-related protein) neurons that are likewise called the arcuate nucleus, or ARC. They are significant for energy homeostasis in the body and also for instigating cravings or hunger on demand.

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‘Group of neurons called AgRP (agouti-related protein) neurons responsible for appetite, may also play a role in depression that outcome from unpredictable, chronic stress. Thus designing a treatment target for AgRP neurons that simultaneously reduces the symptoms of depression as well as avoids the converse side effects of weight gain may help overcome depression.’

Although the exact mechanism is unclear, these AgRP neurons are said to undergo changes in their function like reduced ability to spontaneously fire with altered firing properties upon exposure to chronic, unpredictable stress like one that may erupt in personal and professional lives. This results in depression over time, as demonstrated in both the male and female mouse model of depression.

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Major depression, one of the most common mental health disorders in the United States (as per the National Institute of Mental Health), is characterized by a persistent feeling of sadness and loss of interest, which may lead to a wide range of serious emotional and physical problems. Depression can be hereditary.

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Depression occurs due to alterations in the levels of neurotransmitters in the brain.

Around 17.3 million adults experience at least one episode of depression with higher prevalence rates among 18-25-year-olds. Females face about twice the risk of developing depression than men.

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Inhibition of AgRP neurons using a synthetic small molecule agonist that binds to the neuron receptors increased depression-like behavior in the mice such as reduced desires for rewards like consuming palatable sucrose and sex in mice models.

Subsequently, reversal of classic depressive behaviors was seen on activation of the neurons. The AgRP neurons thus appear to a sensible treatment targets for depression.

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It was also found that the stress-related decrease in AgRP neuron activity produced an increase in the activity of other nearby neuron types in the ARC. As a result of this, the neurons involved in stress & reward in other subregions of the hypothalamus and other parts of the brain are being explored to define the circuitry involved.

Treatment Targets for Depression

"We want to find better ways to treat it, including more targeted treatments that may reduce side effects, which often are significant enough to prompt patients to stop taking them," says Dr. Xin-Yun Lu, chair of the Department of Neuroscience and Regenerative Medicine at MCG at Augusta University and Georgia Research Alliance Eminent Scholar in Translational Neuroscience.

While it's unknown if some of the existing antidepressants happen to impact AgRP neurons, it's possible that new therapies designed to target the neurons could also produce weight gain because of the neurons' role in feeding behavior and metabolism, affirms the study.

Also, elimination of the AgRP neurons may suppress the feeding that would in turn result in anorexia. Hence it is vital to design a treatment target that simultaneously reduces the symptoms of depression as well as avoids the converse side effects.

Source-Medindia