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In a first, growth hormone’s effect on ‘anxiety neurons’ identified

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In a first, growth hormone's effect on 'anxiety neurons' identified

Researchers have identified the specific neurons responsible for controlling how growth hormone affects anxiety and the creation of fear memories, a hallmark of post-traumatic stress disorder. The discovery could lead to a new class of anti-anxiety drugs.

Depression, anxiety, and post-traumatic stress disorder (PTSD) affect millions of people worldwide. While the exact mechanisms underlying these conditions are not fully understood, growing evidence suggests that hormones may affect a person’s susceptibility to them.

A new study by researchers at the University of São Paulo (USP) in Brazil has provided a better understanding of the role of one hormone – growth hormone (GH) – in anxiety, for the first time identifying the neurons responsible for modulating the influence of GH on neuropsychiatric disorders like anxiety, depression, and PTSD.

“Our discovery of the mechanism involving anxiolytic [anxiety-reducing] effects of GH offers a possible, merely chemical, explanation for these disorders, suggesting why patients with more or less GH secretion are more or less susceptible to them,” said José Donato Júnior, corresponding author of the study.

Somatotropic cells of the pituitary gland secrete GH, which is primarily controlled by growth hormone-releasing hormone (GHRH), produced by the hypothalamus to stimulate GH release; somatostatin (SST), produced by various tissues throughout the body to inhibit it; and ghrelin, which is produced by the stomach as part of the hunger response and is protective against hypoglycemia (low blood glucose).

Fear-related disorders like panic disorder, phobias, and PTSD are characterized by a pathological fear response as a result of exposure to strong fear-evoking events, leading to the formation of a ‘fear memory’ in the hippocampus and amygdala. Here, ghrelin plays a role.

“The role of ghrelin in post-traumatic stress has been studied for some time,” said Donato. “Research has shown that ghrelin-induced GH secretion increases in chronic stress, favoring the development of fear memory and post-traumatic stress in the animal’s brain.”

Likewise with SST. While studies have shown that SST-expressing neurons in the amygdala are associated with changes in anxiety and fear memory, whether these neurons are responsive to and mediate the effects of GH to regulate anxiety and fear memory is unknown. That’s what the researchers wanted to investigate.

They found that, in mice, approximately 60% of SST-expressing neurons in the amygdala were directly responsive to GH. In adult male and female mice with the GH receptor gene in SST-expressing neurons knocked out, the male mice displayed increased anxiety-like behavior, whereas females showed no changes in anxiety. In the absence of GH receptors, both sexes exhibited a significant reduction in fear memory.

The research did not provide a reason for the difference between the sexes.

“We believe it may be related to sexual dimorphism,” Donato said. “We know the brain region containing the neurons we studied is a bit different in males and females. Some neurological disorders are also different in men and women, probably not by change.”

The study’s findings suggest that anxiety, post-traumatic stress, and fear memory are different facets of the same brain circuitry.

“All this happens in the same neuron population, which expresses the GH receptor,” said Donato. “In our experiment, fear memory was reduced in mice when we switched the GH receptor off. This means the capacity to form fear memory is impaired. It may be the case that GH contributes to the development of post-traumatic stress.”

The researchers say that the knowledge gained by the study could be used to develop a new class of anxiolytic drugs. And, because GH production reduces as we age, further research should investigate the potential association between GH, SST neurons and neuropsychiatric disorders during aging. However, the researchers’ next step is to look at the role of GH during pregnancy.

“We know one of the peaks in GH productions occurs during pregnancy,” said Donato. “We also know that the prevalence of depression rises in this period owing to post-partum depression. Of course, these disorders also reflect social, economic and other kinds of pressure, but we mustn’t forget that the rise in hormone secretion during and after pregnancy can dysregulate brain functioning, also leading to this kind of mental illness.”

The study was published in the Journal of Neuroscience.

Source: Agência FAPESP

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