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/con … 085696.full.pdf+html

Related Stories

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

May 28, 2013
For several years, the pharmaceutical industry has tried to develop drugs that target a specific neurotransmitter receptor in the brain, the NMDA receptor. This receptor is present on almost every neuron in the human brain ...

Rewriting a receptor's role: Synaptic molecule works differently than thought

February 19, 2013
(Medical Xpress)—In a pair of new papers, researchers at the University of California, San Diego School of Medicine and the Royal Netherlands Academy of Arts and Sciences upend a long-held view about the basic functioning ...

Promising new finding for therapies to treat persistent seizures in epileptic patients

January 16, 2013
In a promising finding for epileptic patients suffering from persistent seizures known as status epilepticus, researchers reported today that new medication could help halt these devastating seizures. To do so, it would have ...

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

Study finds walnuts may promote health by changing gut bacteria

July 28, 2017
Research led by Lauri Byerley, PhD, RD, Research Associate Professor of Physiology at LSU Health New Orleans School of Medicine, has found that walnuts in the diet change the makeup of bacteria in the gut, which suggests ...

Green tea ingredient may ameliorate memory impairment, brain insulin resistance, and obesity

July 28, 2017
A study published online in The FASEB Journal, involving mice, suggests that EGCG (epigallocatechin-3-gallate), the most abundant catechin and biologically active component in green tea, could alleviate high-fat and high-fructose ...

Manipulating a type of brain cell gets weight loss results in mice

July 28, 2017
A new study has found something remarkable: the activation of a particular type of immune cell in the brain can, on its own, lead to obesity in mice. This striking result provides the strongest demonstration yet that brain ...

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

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.