Neurochemical traffic signals may open new avenues for the treatment of schizophrenia

June 5, 2013

Researchers at Boston University School of Medicine (BUSM) have uncovered important clues about a biochemical pathway in the brain that may one day expand treatment options for schizophrenia. The study, published online in the journal Molecular Pharmacology, was led by faculty within the department of pharmacology and experimental therapeutics at BUSM.

Patients with schizophrenia suffer from a life-long condition that can produce delusions, disordered thinking, and breaks with reality. A number of treatments are available for schizophrenia, but many patients do not respond to these therapies or experience side effects that limit their use.

This research focused on key components of the brain known as . These receptors are located on nerve cells in the brain and serve as biochemical gates that allow (electrical charges) to enter the cell when a neurotransmitter, such as glutamate, binds to the receptor. Proper activation of these receptors is critical for , memory and learning, including the transfer of short-term memory into long-term storage. Patients with schizophrenia have poorly functioning or "hypoactive" NMDA receptors, suggesting the possibility of treatment with drugs that positively affect these receptors. Currently the only way to enhance NMDA receptor function is through the use of agents called agonists that directly bind to the receptor on the outer surface of the cell, opening the gates to calcium ions outside the cell.

In this study, the researchers discovered a novel "non-canonical" pathway in which NMDA receptors residing inside the cell are stimulated by a neuroactive steroid to migrate to the cell surface (a process known as trafficking), thus increasing the number of receptors available for glutamate activation. The researchers treated from the with the novel steroid pregnenolone sulfate (PregS) and found that the number of working NMDA receptors on the cell surface increased by 60 to 100 percent within 10 minutes. The exact mechanism by which this occurs is not completely clear, but it appears that PregS increases calcium ions within the cell, which in turn produces a green light signal for more frequent trafficking of NMDA receptors to the cell surface.

Although still in the early stages, further research in this area may be instrumental in the development of treatments not only for schizophrenia, but also for other conditions associated with malfunctioning NMDA receptors, such as age-related decreases in memory and learning ability.

Explore further: Scientists advance understanding of brain receptor; may help fight neurological disorders

More information: molpharm.aspetjournals.org/content/early/2013/05/28/mol.113.085696.full.pdf+html

Related Stories

Unique protein bond enables learning and memory

October 30, 2012

Two proteins have a unique bond that enables brain receptors essential to learning and memory to not only get and stay where they're needed, but to be hauled off when they aren't, researchers say.

New drug target for Alzheimer's, stroke discovered

October 11, 2011

A tiny piece of a critical receptor that fuels the brain and without which sentient beings cannot live has been discovered by University at Buffalo scientists as a promising new drug target for Alzheimer's and other neurodegenerative ...

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.