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Link between depression and inflammatory response found in mice
Date:12/20/2010

Vanderbilt University researchers may have found a clue to the blues that can come with the flu depression may be triggered by the same mechanisms that enable the immune system to respond to infection.

In a study in the December issue of Neuropsychopharmacology, Chong-Bin Zhu, M.D., Ph.D., Randy Blakely, Ph.D., William Hewlett, M.D., Ph.D., and colleagues activated the immune system in mice to produce "despair-like" behavior that has similarities to depression in humans.

"Many people exhibit signs of lethargy and depressed mood during flu-like illnesses," said Blakely, director of the Vanderbilt Center for Molecular Neuroscience. "Generally these have been treated as just a consequence of being physically ill, but we think there is likely to be something more brain-centric at work here."

Blakely and his colleagues previously reported that inflammatory cytokines can enhance the activity of the serotonin transporter (SERT), which regulates the supply of the neurotransmitter serotonin in the synapse, or gap between nerve cells.

Elevations in SERT activity remove serotonin from brain synapses at an enhanced rate and, based on studies in animal models and man, would be predicted to increase the risk for mood and anxiety disorders. Indeed, a class of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs) Prozac, Zoloft, etc. work by blocking the ability of SERT to eliminate serotonin.

In the current study in mice, the researchers triggered pro-inflammatory cytokine production. Within 30 to 60 minutes, SERT was activated in the brain and the animals displayed despair-like behavior.

Remarkably, this behavior was not observed when cytokine production was triggered in mice lacking the SERT gene. Similarly, a drug that blocks inflammatory molecule signaling also prevented stimulation of SERT and the despair behavior. "It's as if these inflammatory molecules are an 'anti-Prozac,'" Blakely said.

In their paper, t
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Contact: Bill Snyder
bill.snyder@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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