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Major stress and chronic depression often go together. Unfortunately, together they cause the loss of brain volume which contributes to emotional and cognitive impairment. Researchers have now discovered that this occurs as a result of a single genetic switch that triggers loss of brain connections in human and depression in animal models.
The genetic switch called a transcription factor represses the expression of several genes that are needed for the creation of synaptic connections between brain cells. This causes a 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 Ronal Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of neurobiology and of pharmacy. “We show that circuits normally involved in motion, as well as cognition, are disrupted when this single transcription factor is activated.”
The researchers analyzed donated brain tissue of depressed and non-depressed people available at a brain bank. They looked for patterns of gene activation. The depressed people had lower levels of expression in genes required for the structure of brain synapses. They discovered that five of the genes could be regulated by a single transcription factor called GATA1. When tested on rodents, the activation of GATA1 caused depressive-like symptoms. So GATA1 is connected with brain synapse loss and depression.
“We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies,” said Duman.
Source: MedicalNewsToday, Yale University, Nature Medicine
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