Archive for the ‘antidepressant’ Category

Scientists probing the link between depression and a hormone that controls hunger have found that the hormone’s antidepressant activity is due to its ability to protect newborn neurons in a part of the brain that controls mood, memory, and complex eating behaviors. Moreover, the researchers also showed that a new class of neuroprotective molecules achieves the same effect by working in the same part of the brain, and may thus represent a powerful new approach for treating depression.

“Despite the availability of many antidepressant drugs and other therapeutic approaches, major depression remains very difficult to treat,” says Andrew Pieper, associate professor of psychiatry and neurology at the University of Iowa Carver College of Medicine and Department of Veterans Affairs, and co-senior author of the study.

In the new study, Pieper and colleagues from University of Texas Southwestern Medical Center led by Jeffrey Zigman, associate professor of internal medicine and psychiatry at UT Southwestern, focused on understanding the relationship between depression, the gut hormone ghrelin, and the survival of newborn neurons in the hippocampus, the brain region involved in mood, memory, and eating behaviors.

“Not only did we demonstrate that the P7C3 compounds were able to block the exaggerated stress-induced depression experienced by mice lacking ghrelin receptors, but we also showed that a more active P7C3 analog was able to complement the antidepressant effect of ghrelin in normal mice, increasing the protection against depression caused by chronic stress in these animals,” Zigman explains.

“The P7C3 compounds showed potent antidepressant activity that was based on their neurogenesis-promoting properties,” Pieper adds. “Another exciting finding was that our experiments showed that the highly active P7C3 analog acted more rapidly and was more effective [at enhancing neurogenesis] than a wide range of currently available antidepressant drugs.”

The findings suggest that P7C3-based compounds may represent a new approach for treating depression. Drugs based on P7C3 might be particularly helpful for treating depression associated with chronic stress and depression associated with a reduced response to ghrelin activity, which may occur in conditions such as obesity and anorexia nervosa.

Future studies, including clinical trials, will be needed to investigate whether the findings are applicable to other forms of depression, and determine whether the P7C3 class will have antidepressant effects in people with major depression.

The hippocampus is one of the few regions in the adult brain where new neurons are continually produced – a process known as neurogenesis. Certain neurological diseases, including depression, interfere with neurogenesis by causing death of these new neurons, leading to a net decrease in the number of new neurons produced in the hippocampus.

Ghrelin, which is produced mainly by the stomach and is best known for its ability to stimulate appetite, also acts as a natural antidepressant. During chronic stress, ghrelin levels rise and limit the severity of depression caused by long-term stress. When mice that are unable to respond to ghrelin experience chronic stress they have more severe depression than normal mice.

In the new study, Pieper and Zigman’s team showed that disrupted neurogenesis is a contributing cause of depression induced by chronic stress, and that ghrelin’s antidepressant effect works through the hormone’s ability to enhance neurogenesis in the hippocampus. Specifically, ghrelin helps block the death of these newborn neurons that otherwise occurs with depression-inducing stress. Importantly, the study also shows that the new “P7C3-class” of neuroprotective compounds, which bolster neurogenesis in the hippocampus, are powerful, fast-acting antidepressants in an animal model of stress-induced depression. The results were published online April 22 in the journal Molecular Psychiatry.

Potential for new antidepressant drugs

The neuroprotective compounds tested in the study were discovered about eight years ago by Pieper, then at UT Southwestern Medical Center, and colleagues there, including Steven McKnight and Joseph Ready. The root compound, known as P7C3, and its analogs protect newborn neurons from cell death, leading to an overall increase in neurogenesis. These compounds have already shown promising neuroprotective effects in models of neurodegenerative disease, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and traumatic brain injury. In the new study, the team investigated whether the neuroprotective P7C3 compounds would reduce depression in mice exposed to chronic stress, by enhancing neurogenesis in the hippocampus.

http://now.uiowa.edu/2014/04/protecting-new-neurons-reduces-depression-caused-stress

Advertisements

crf

Scientists have used one of the world’s most powerful X-ray machines to identify the molecule responsible for feelings of stress, anxiety and even depression.

The pituitary gland is known to the medical world as a key player in stress and anxiety, as it releases stress chemicals in the blood.

However, scientists have now discovered that the protein receptor CRF1 is responsible for releasing hormones which can cause anxiety and depression over extended periods of time. The protein receptor is found in the brain and controls our response to stress. When it detects stress molecules released by the hypothalamus, it releases these hormones.

The study, conducted by drug company Heptares Therapeutics, was published in the Nature journal on 17 July.

Researchers used a particle accelerator called the Diamond Light Source to understand the structure of CRF1. The X-ray machine’s powerful beams illuminated the protein’s structure, according to the Sunday Times, including a crevice that could become a new target for drug therapy.

The information gained from this study will be used to design small molecule drugs that fit into this new pocket to treat depression.

Speaking to the Sunday Times, Dr Fiona Marshall, Chief Scientific Officer at Heptares Therapeutics, said: “Now we know its shape, we can design a molecule that will lock into this crevice and block it so that CRF1 becomes inactive — ending the biochemical cascade that ends in stress.”

Writing on Diamond’s website, Dr. Andrew Dore, a senior scientist with Heptares added that the structure of the protein receptor “can be used as a template to solve closely related receptors that open up the potential for new drugs to treat a number of major diseases including Type 2 diabetes and osteoporosis”.

Thanks to Tracy Lindley for bringing this to the attention of the It’s Interesting community.

http://www.independent.co.uk/news/science/scientists-discover-the-molecule-responsible-for-causing-feelings-of-depression-8724471.html