As the largest resource of information specific to women's brain health, we are sure you will find what you are looking for, and promise that you will discover new information.
Published on: November 14, 2014
by Kristine Fischer for Healthline:
Whether a single protein in the brain is activated — or not — seems to make some people more vulnerable to depression than others.
A study performed at the Icahn School of Medicine at Mount Sinai and published in the journal Nature sheds light on why people suffer from depression and how to treat them. It shifts the focus away from brain chemicals like serotonin and dopamine, which are the typical targets of depression research.
“Our findings are distinct from serotonin and other neurotransmitters previously implicated in depression or resilience against it,” said Dr. Eric J. Nestler, Ph.D., chairman of the department of neuroscience and director of the Friedman Brain Institute at the Icahn School of Medicine, in a press statement.
Researchers already know that the protein beta-catenin plays many roles in the human body. Nestler examined mice that were exposed to chronic stress and found that the protein in a part of the brain called the nucleus accumbens (NAc) makes some people more resilient than others.
When the researchers blocked beta-catenin in mice that showed resilience to depression, the mice became more susceptible to stress. Upon activating the protein, the mice became better protected from stress. The researchers also found that the protein was suppressed in the brain tissue of depressed humans.
Caroline Dias, an M.D.-Ph.D. student at the Icahn School of Medicine who teamed up with Nestler on the investigation, said that the finding in humans was significant because it showed decreased activation of beta-catenin in depressed humans, regardless of whether they were taking antidepressants when they died.
“This implies that the antidepressants were not adequately targeting this brain system,” she said in a press statement.
The Science of Depression
Almost all nerve cells in the NAc region are known as medium spiny neurons, which are broken down into two types based on how they interact with dopamine: D1 receptors and D2 receptors. Beta-catenin interacts with the D2 receptors. The researchers looked at the how well the D2 neurons handled deficits in reward and motivation that are linked to depression, as well as enhancements that would protect them from stress.
They examined what happens when beta-catenin is activated, and found that the protein is linked with Dicer1, an enzyme that makes microRNAs, which are tiny molecules that control whether or not genes are expressed.
Nestler’s team identified a cluster of microRNAs that are created by resilience triggered by beta-catenin. Some of these microRNAs might make interesting medicinal agents because some can cross the blood/brain barrier and enter the brain.
“While we have identified some of the genes that are targeted, future studies will be key to see how these genes affect depression,” Dias said.
Nestler said researchers aren’t sure why depressed patients have lower beta-catenin activity in their brains.
“I think it is likely not to be genetic: no mutations in genes that control beta-catenin activity have been demonstrated in human depression,” he said.
He said it’s possible that differences in the way an individual responds to stress have differing effects on beta-catenin activity, which can then lead to depression.
A New Way to Treat Depression?
This study is the first to show that higher beta-catenin activity makes you more resilient. It’s also the first to report a link between beta-catenin and microRNA production. In the future, depression treatment could be focused on this pathway in order to boost a person’s resilience in the face of stress.
Past treatments have focused on ways to undo the bad effects of stress after the fact. The new findings provide a pathway to generate “novel antidepressants that instead activate mechanisms of natural resilience,” Nestler said.
Nestler said that beta-catenin itself would not be a good drug target for depression because it is expressed in all our organs. It has different gene targets in different cell types, however, so he’s looking to pinpoint those targets that have antidepressant-like effects.
“We view this protein (Β-catenin) as a path toward antidepressant treatment that is distinct from that of SSRIs and other currently available medications,” Nestler said. He believes this is important because almost all of the antidepressants used today have the same mechanism of action that was first discovered six decades ago.
“If we want a medication that works better than current ones, we need ones with a different mechanism,” he added.
Diagnosis of dementia is made via cognitive function tests such as the Mini-Mental State Examination (MMSE) and medical imaging systems at hospitals, a fairly large system for the purpose. As the population ages, an increasing number of...
In the past eight years, the Canadian Institutes of Health Research (2010), the European Commission (2014), and more recently the National Institutes of Health (2015), have announced policies requiring basic and clinical researchers to integrate sex as...
Two strains of human herpesvirus—human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7)—are found in the brains of individuals with Alzheimer’s disease at levels up to twice as high as in those without Alzheimer’s, according to...
The material presented through the Think Tank feature on this website is in no way intended to replace professional medical care or attention by a qualified practitioner. WBHI strongly advises all questioners and viewers using this feature with health problems to consult a qualified physician, especially before starting any treatment. The materials provided on this website cannot and should not be used as a basis for diagnosis or choice of treatment. The materials are not exhaustive and cannot always respect all the most recent research in all areas of medicine.