Navigation Links
Sticky blood protein yields clues to autism
Date:3/4/2008

Many children with autism have elevated blood levels of serotonin a chemical with strong links to mood and anxiety. But what relevance this hyperserotonemia has for autism has remained a mystery.

New research by Vanderbilt University Medical Center investigators provides a physical basis for this phenomenon, which may have profound implications for the origin of some autism-associated deficits.

In an advance online publication in the Journal of Clinical Investigation, Ana Carneiro, Ph.D., and colleagues report that a well-known protein found in blood platelets, integrin beta3, physically associates with and regulates the serotonin transporter (SERT), a protein that controls serotonin availability.

Autism, a prevalent childhood disorder, involves deficits in language, social communication and prominent rigid-compulsive traits. Serotonin has long been suspected to play a role in autism since elevated blood serotonin and genetic variations in the SERT have been linked to autism.

Alterations in brain serotonin have also been associated with anxiety, depression and alcoholism; antidepressants that block SERT (known as SSRIs, or selective serotonin reuptake inhibitors) block SERTs ability to sweep synapses clean of serotonin.

Working in the lab of Randy Blakely, Ph.D., Carneiro was searching for proteins that interact with SERT that might contribute to disorders where serotonin signaling is altered.

Levels of SERT in the brain are actually quite low, so we decided to see what progress we could make with peripheral cells that have much higher quantities, said Blakely, the Allan D. Bass Professor of Pharmacology and director of the Vanderbilt Center for Molecular Neuroscience. This took us to platelets.

In platelets, SERTs accumulate serotonin produced in the gut. SSRIs or genetic deletion of SERT in animals prevents serotonin uptake in the platelet.

Prior research had fingered the integrin beta3 gene as a determinant of blood serotonin levels and, independently, as a risk factor for autism, Blakely said.

In the current study, Carneiro identified a large set of proteins that stick to SERT, presuming they might control SERT activity. One of these turned out to be integrin beta3.

Once they confirmed a physical relationship between the two proteins, Blakelys team investigated whether the interaction can change SERT activity. They found that cells lacking integrin beta3 exhibit reduced serotonin uptake and that integrin beta3 activation or a human integrin beta3 mutation greatly enhances serotonin uptake.

We found that integrin beta3 can put the serotonin transporter into high gear, said Blakely. Notably, Edwin Cook, M.D., at the University of Illinois at Chicago and a co-author on the study, had shown that the same integrin beta3 mutation that elevates SERT activity also predicts elevated blood serotonin.

Most investigators studying this integrin beta3 mutation have focused on how its high activity state changes platelet clotting and never looked at its impact on serotonin levels or SERT function, explained Carneiro. Now they have a reason to.

We dont think the platelet itself contributes to autism, said Blakely, but rather we believe that the brains serotonin transporter may be controlled by integrin proteins in a very similar manner.

Carneiro and Blakely believe that too much SERT activity imposed by abnormal integrin interactions could restrict availability of serotonin in the brain during development, as well as in the adult.

What is even more striking is that this is the second time we have found elevated SERT activity associated with autism, said Blakely. In a 2005 study, Blakely and Vanderbilt collaborator James Sutcliffe, Ph.D., identified mutations in the SERT gene that triggered elevated SERT activity.

Carneiro is now hot on the trail of integrin interactions with brain SERT as well as engineering mice that express human integrin beta3 mutations.

At a February Keystone Conference, Blakely described preliminary studies with mice that his lab has engineered to express hyperactive SERT mutations. Together, these new animal models offer an unprecedented opportunity to peel away the complexity of autism and possibly develop new therapies, he said.

This research also may uncover new ways of treating depression. Current antidepressant mechanisms still essentially work in the same way they did 25 years ago by targeting transporter uptake of neurotransmitter directly, Carneiro said. Now we may have a completely new way to go about it.


'/>"/>

Contact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

Related medicine news :

1. Actor Rob Brown Rushes to Gain Ground Against Blood Cancer
2. Common Rheumatoid Arthritis Drug Wont Raise Blood Cancer Risk
3. Researchers find possible target to treat deadly bloodstream infections
4. New blood marker may predict prostate cancer spread
5. Drugs used for cancer-associated anemia linked with increased risk of blood clots, death
6. Blood Clots in Legs, Lungs Predispose Patients to Repeat Episodes
7. Mechanism of blood clot elasticity revealed in high definition
8. Indiana Blood Center Signs BIO-key(R) Contract
9. Current Blood Sugar Control Test Results Inaccurate
10. Another way to grow blood vessels
11. Study identifies another strategy for normalizing tumor blood supply
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/7/2016)... ... December 07, 2016 , ... A quote from Dr. Edward Hallowell, host ... social media that offer a rare glimpse into the mind of those people with ... York Times bestselling author, has described people with ADHD as having “Ferrari engines for ...
(Date:12/7/2016)... ... December 07, 2016 , ... The ... offices located in South Lyon, Dewitt, Williamston, East Lansing, Ann Arbor, and Farmington ... needs treatment for a brain tumor. , Jason Bauer and his family are ...
(Date:12/7/2016)... ... , ... A. Kevin Spann Insurance, a New York-based firm offering insurance and ... a charity drive to raise funds that will benefit the Marine Corps League. , ... Navy FMF Corpsmen. Working closely with the MCL, the A. Kevin Spann team plans ...
(Date:12/7/2016)... ... 07, 2016 , ... Delete® - Tattoo Removal and Laser Salon Offers Delightful ... Save Up To 33% Off Botox® and Juvederm® Products Now Through December 31, 2016 ... Delightful Deals on Botox® and Juvederm® just in time for the holiday ...
(Date:12/7/2016)... ... December 07, 2016 , ... Gensuite is honored to be ... Best New Product Launch category. Gensuite’s entry on their EZ Scan feature detailed ... Events & Training Group is a professional event and training provider based in ...
Breaking Medicine News(10 mins):
(Date:12/7/2016)... NORTH READING, Mass. , Dec. 7, 2016 ... Track and Trace Network for connecting the Life ... from the global marketplace, today announced that Tjoapack ... 50+ European pharmaceutical manufacturing customers comply with the ... Supply Chain Security Act (DSCSA) in 2017 and ...
(Date:12/7/2016)... According to a new market research report "Clinical Decision Support Systems Market ... Type (Therapeutic, Diagnostic), User Interactivity (Active, Passive), Application - Forecasts to 2021" ... Million by 2021 from USD 856.3 Million in 2016, at a CAGR ... ... MarketsandMarkets Logo ...
(Date:12/7/2016)... 7, 2016 Today, Stock-Callers.com presents four ... JAZZ ), Anthera Pharmaceuticals Inc. (NASDAQ: ANTH ... AveXis Inc. (NASDAQ: AVXS ). From its peak ... 37% to reach a level equal to what it saw ... approximately 14% for the year, it has still out-performed other ...
Breaking Medicine Technology: