Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Depression linked to previously unknown dopamine regulator

29.07.2005


Finding advances hope for potential new target for antidepressants



Researchers from Harvard Medical School have found a molecule that is unexpectedly involved in dopamine signaling, and in a manner that supports the potential of dopamine as an alternative target for treating depression. The results provide evidence that there is a molecular link between impaired dopamine signaling and depression, which affects 16 percent of the adult population in the United States. The research appears in the July 29 issue of Cell.

Li-Huei Tsai, Harvard Medical School (HMS) professor of pathology, HMS research fellow Sang Ki Park, and colleagues worked with mice and found a novel function for the molecule Par-4 (prostate apoptosis response 4)--as a binding partner for dopamine receptor D2. When mice deficient in Par-4 were subjected to stress, they showed depression-like behaviors, proposing Par-4–as a molecular link between dopamine signaling and depression. Par-4 was previously implicated as a proapoptotic factor in neurodegenerative diseases such as Alzheimer’s disease. These new findings reveal an unexpected role for Par-4 in the dopamine system and present a rare glimpse of molecular mechanisms behind clinical depression.


"Current antidepression therapies are mostly based on the deficiency or imbalance of the serotonin and noradrenaline systems. Our study highlights the importance of the dopamine system, a less appreciated target in the current antidepression therapies," said Tsai, also a Howard Hughes Medical Institute investigator.

Although the cause of depression is multifaceted, a hypothesis based on deficiency or imbalance of serotonin and/or noradrenaline as the root of depression has been a central topic of research. Drugs that currently treat depression (SSRIs and MAOIs, which acutely modify levels of serotonin or noradrenaline at the synapse) have significant delays before becoming effective, and a large percentage of people are resistant to the current therapies, leaving room for improvement of therapeutic strategies.

The brain’s mood, reward, and motivation circuits are mainly governed by dopamine and have been regarded as potential alternative targets for treating depression. Many of these functions are integrated by the medium spiny neurons of the striatum, which lie below the cortex of the brain and respond to dopamine. Dopamine exerts its function in target cells through five known subtypes of dopamine receptors to regulate motor control, stereotypic behaviors, arousal, mood, motivation, and endocrine function. Impairment in the function of dopamine D2 receptor is implicated in various neuropsychiatric disorders including schizophrenia and drug addiction.

Understanding the details of the modulatory events in D2 dopamine receptor–mediated intracellular signaling may provide novel therapeutic targets for treating various associated disorders.

Leah Gourley | EurekAlert!
Further information:
http://www.hms.harvard.edu

More articles from Life Sciences:

nachricht Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung

nachricht Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>