Shrinking Brains – Depression and Stress – Yale

Yale team discovers how stress and depression can shrink the brain

http://news.yale.edu/2012/08/12/yale-team-discovers-how-stress-and-depression-can-shrink-brain

Major depression or chronic stress can cause the loss of brain volume, a condition that contributes to both emotional and cognitive impairment. Now a team of researchers led by Yale scientists has discovered one reason why this occurs — a single genetic switch that triggers loss of brain connections in humans and depression in animal models.

The findings, reported in the Aug. 12 issue of the journal Nature Medicine, show that 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, which in turn could contribute to loss of brain mass in the prefrontal cortex.

“We wanted to test the idea that stress causes a loss of brain synapses in humans,” said senior author Ronald Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of neurobiology and of pharmacology. “We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.”

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 discovered that at least five of these genes could be regulated by a single transcription factor called GATA1. When the transcription factor was activated, 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.

Duman theorizes that genetic variations in GATA1 may one day help 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.

The study was funded by the National Institutes of Health and the Connecticut Department of Mental Health and Addiction Services.

Other Yale authors of the paper are Bhavya Voleti, Pawel Licznerski, Ashley Lepack, and Mounira Banasr.

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Further Reading

Progress in allergy signal research on mast cells: regulation of allergic airway inflammation through toll-like receptor 4-mediated modification of mast cell function.

http://www.ncbi.nlm.nih.gov/pubmed/18360088

Source

Department of Immunology, Graduate School of Medicine, Chiba University, Japan. yamamasa@faculty.chiba-u.jp

Abstract

In a mouse experimental asthma model, the administration of bacterial lipopolysaccharide (LPS), particularly at low doses, enhances the levels of ovalbumin (OVA)-induced eosinophilic airway inflammation. In an effort to clarify the cellular and molecular basis for the LPS effect, we demonstrate that the OVA-induced eosinophilic inflammation in the lung is dramatically increased by administration of LPS at the priming phase in wild-type mice, whereas such an increase was not observed in mast cell deficient mice. Adoptive transfer of bone marrow-derived mast cells (BMMC) from wild type but not from Toll-like receptor 4 (TLR4)-deficient mice restored the increased eosinophilic inflammation in mast cell-deficient mice. Moreover, in vitro analysis revealed that treatment of BMMC with LPS resulted in sustained up-regulation of GATA1 expression and increased production of Th2 cytokines (IL-4, IL-5, and IL-13) upon restimulation. Thus, mast cells appear to control allergic airway inflammation after their activation and modulation through TLR4-mediated induction of GATA1 proteins and subsequent increase in Th2 cytokine production.

This entry was posted in Allergy, Asthma, Autism, co-morbid, Immune System, Inflammation, Mice, Neurology, Physiology and tagged , , , , , , , , , , . Bookmark the permalink.

1 Response to Shrinking Brains – Depression and Stress – Yale

  1. Pingback: Seniors Mental Health & Depression | tycunepercussion.com

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