Posts Tagged Brain Cells

Stress, Depression Reduce Brain Volume Thanks to Genetic ‘Switch’


Stress, Depression Reduce Brain Volume Thanks to Genetic 'Switch' Scientists have known that stress and depression can cause the brain to retract or lose volume, a condition associated with both emotional and cognitive impairment. Now, a new study discovers why this occurs.

Yale scientists have found that the deactivation of a single genetic switch can instigate a cascading loss of brain connections in humans and depression in animal models.

Researchers say the genetic switch, known as a transcription factor, represses the expression of several genes that are necessary for the formation of synaptic connections between brain cells. The loss of connections, in turn, can contribute to loss of brain mass in the prefrontal cortex, say the scientists.

“We wanted to test the idea that stress causes a loss of brain synapses in humans,” said senior author Ronald Duman, Ph.D. “We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.”

In the study, the research team analyzed tissue of depressed and non-depressed patients donated from a brain bank and looked for different patterns of gene activation.

The brains of patients who had been depressed exhibited lower levels of expression in genes that are required for the function and structure of brain synapses.

Lead author and postdoctoral researcher H.J. Kang, Ph.D., discovered that at least five of these genes could be regulated by a single transcription factor called GATA1.

When the transcription factor was activated in animal models, rodents exhibited depressive-like symptoms, suggesting GATA1 plays a role not only in the loss of connections between neurons but also in symptoms of depression.

This finding of genetic variations in GATA1 may help researchers identify people at high risk for major depression or sensitivity to stress.

“We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies,” Duman said.

Source: Yale University

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Animal Study Suggests New Class of Antioxidants May Be Beneficial for Parkinson’s


Animal Study Suggests New Class of Antioxidants May Be Beneficial for Parkinson’s A new powerful class of antioxidants may provide relief from Parkinson’s in the future.

The medication, called synthetic triterpenoids, blocked development of Parkinson’s disease in an animal model.

The trial is discussed in the journal Antioxidants & Redox Signaling , as authored by Dr. Bobby Thomas, a neuroscientist at the Medical College of Georgia.

Thomas and his colleagues were able to block the death of dopamine-producing brain cells that occurs in Parkinson’s by using the drugs to bolster Nrf2, a natural antioxidant and inflammation fighter.

Researchers know that stressors from a variety of sources, be it trauma, insect bites or the simple aging process increases oxidative stress causing the body to respond with inflammation — as a part of the natural healing process.

“This creates an environment in your brain that is not conducive for normal function,” Thomas said.

“You can see the signs of oxidative damage in the brain long before the neurons actually degenerate in Parkinson’s.”

Nrf2, the master regulator of oxidative stress and inflammation, is – inexplicably – significantly decreased early in Parkinson’s. In fact, Nrf2 activity declines normally with age.

“In Parkinson’s patients you can clearly see a significant overload of oxidative stress, which is why we chose this target,” Thomas said. “We used drugs to selectively activate Nrf2.”

Researchers looked at a number of antioxidants already under study for a wide range of diseases from kidney failure to heart disease and diabetes, and found triterpenoids to be the most effective on Nrf2.

Co-author Dr. Michael Sporn, Professor of Pharmacology, Toxicology and Medicine at Dartmouth Medical School, chemically modified the agents so they could permeate the protective blood-brain barrier.

Researchers found that in both human neuroblastoma and mouse brain cells they were able to document an increase in Nrf2 in response to the synthetic triterpenoids.

Their preliminary evidence indicates the synthetic triterpenoids also increase Nrf2 activity in astrocytes, a brain cell type which nourishes neurons and hauls off some of their garbage.

The drugs didn’t protect brain cells in an animal where the Nrf2 gene was deleted, more proof that that Nrf2 is the drugs’ target.

Researchers are now studying the impact of synthetic triterpenoids in an animal model genetically programmed to acquire PD slowly, as humans do.

Source: Medical College of Georgia

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