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Anger Gene (video)
February 04, 2003

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Interviewee: Evan Deneris, Case Western Reserve University.

Video is 1 min 42 sec long. Please be patient while it loads enough to start playing.

Produced by Sanjanthi Velu

Copyright © ScienCentral, Inc., with additional footage courtesy Columbia Pictures.

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Why do some people get angry or anxious about the smallest things?

As this ScienCentral News video reports, it could be because of a missing gene that affects their brain.


Angry Mice

It’s normal for us to feel angry or anxious. They are normal behaviors that help us respond to “a challenging or threatening environment”, says Dr. Evan Deneris, professor of neuroscience at Case Western Reserve University. But, there are limits. He cautions, “if anxiety and aggression become excessive then that will be fairly counter-productive and prevent normal social interactions.”

Deneris and his colleagues have been studying the issue. They report that they have found a gene that regulates normal levels of anxiety and aggression. In a study published in the journal Neuron, the researchers explain that when the gene called PET-1 is removed or “knocked-out” in mice, the mice display a greater level of anxiety and aggression as adults than do normal animals.

Deneris and colleagues had found earlier that the PET-1 gene was active only in a certain kind of nerve cell or neuron in the brain that produced serotonin. Serotonin is a brain chemical that acts as a neurotransmitter or chemical messenger between nerve cells. Serotonin is also important for influencing many neural circuits that control behaviors such as anxiety, aggression, perception, learning, memory, sleep-wake patterns, and other emotions and moods. People who do not produce enough serotonin can suffer from mood disorders like depression and anxiety.

The chemical is so important; we start making it even before we are born. Deneris says, “In humans, serotonin neurons first appear roughly in the middle of the first trimester.”

To learn exactly what was going on inside the brain, Deneris and his team chose to study mice. Despite their size, mice have a lot in common with people, especially where their genes are concerned.

They specially bred mice without the PET-1 gene, and studied their serotonin neuron development. They found that most of the serotonin neurons were missing and the few that did remain were abnormal. “So in the absence of this gene the entire serotonin system is defective,” says Deneris. And according to him that leads to, “low levels of serotonin throughout the developing adult brain in the mutant mice”.

The researchers also actually watched both the genetically modified mice and the normal mice to see how they behave. In one test they put an unfamiliar mouse in with the test mouse. Then, they watched how each mouse behaved. They found the normal mice explored and investigated the intruder by sniffing and chasing it around the cage. Sometimes, they even attacked the intruder but they would normally “wait many minutes before attacking and some of them would never attack”, says Deneris.

However, he says, the mice without the gene “would attack within ten seconds of being introduced to the intruder mouse.” Also, the attacks were more severe and happened more often.

In another test, the researchers measured the amount of time the mice spent in open, unprotected areas of a test chamber compared to closed, protected areas. Deneris says its normal for a mouse to spend most of its time in the protected area to avoid threats, but that it also has a natural tendency to want to explore. They found the modified mice never ventured into the unprotected areas. Instead they remained exclusively in the protected areas. To Deneris this suggests the modified mice are more anxious.

Humans have a gene that, according to Deneris, “is nearly identical to the PET-1 gene” found in the mouse. However, he cautions they don’t yet know whether the human version functions in the same way as the mouse gene.

He says, “given the strong similarities between the serotonin system in the mouse and the serotonin system in the human, we would not be surprised if the human version of PET-1 is performing a similar function in the human brain.” He notes that these mice without the gene could be used to learn even more. For instance, he says they could be used as a new and novel animal model for screening possible new drugs and treatments for aggression and anxiety. Also, they could be used for studying psychiatric disorders that involve the serotonin system.

This study was funded by the National Institute of Mental Health.



by Sanjanthi Velu


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