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Mouse Study Reveals Second Serotonin-Making Gene

German scientists have identified a second enzyme that is involved in making serotonin, a brain chemical associated with depression. And the genetic hardware of this newly identified enzyme is detected primarily in the brain, according to their mouse study reported in the January 3rd issue of the journal Science.

The findings suggest that all past efforts to identify genetic reasons for mental disorders linked to abnormal serotonin production have focused on the wrong gene, according to Dr. Diego J. Walther of the Max Delbruck Center for Molecular Medicine in Berlin-Buch.

[...] Serotonin synthesis occurs in a handful of extremely important neurons in the brain and in some cells of the gastrointestinal tract, Walther explained in an interview with Reuters Health.

"This is common knowledge in the serotonin field, but it was believed for decades that only one enzyme commits the rate-limiting step in the biosynthesis in all tissues. However, we have discovered a second tryptophan hydroxylase enzyme," added the researcher. A rate-limiting step is the slowest step involved in a multiple-step chemical reaction; this step determines the rate at which a reaction occurs.

"Moreover, we were able to elucidate that this second enzyme is the source for serotonin in neurons, and not the formerly known enzyme (Tph-1), which we've found to synthesize serotonin most prominently in the gut of adult vertebrates," said Walther.

"Therefore, our findings (have) opened a door to a completely new research area, and to our understanding of the biosynthesis of a compound related to a multitude of mood-controlling effects," he added.

In the study, the investigators generated mice genetically deficient in Tph1. These mice lacked any serotonin outside the brain except in the duodenum, the part of the small intestine closest to the stomach, where levels were only about 4% of normal.

However, brain regions known to generate serotonin expressed normal amounts of the neurotransmitter in the mutant mice, and the animals exhibited behavior similar to that of non-mutant mice in tests associated with serotonin-related behavior.

Moreover, the RNA of a second enzyme, Tph2, was distinct from that of Tph1, according to the report. When examining total RNA from the brain stem of normal mice, they observed that Tph2 was expressed at levels 150 times greater than that of Tph1.

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Date: 2003-01-09 02:31 am (UTC)
From: [identity profile] droid-1.livejournal.com
That would be so cool, if they find out how to fix depression!

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