Navigation Links
New Light on Working of Brain Networks

A report in the Journal Cell (April 20 from the researchers from Yale School of Medicine and University of Crete School of Medicine has for the first time found evidence of a// molecular mechanism that dynamically alters the strength of higher brain network connections.

This discovery may help the development of drug therapies for the cognitive deficits of normal aging, and for cognitive changes in schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder (ADHD).

“Our data reveal how the brain’s arousal systems influence the cognitive networks that subserve working memory—which plays a key role in abstract thinking, planning, and organizing, as well as suppressing attention to distracting stimuli,” said Amy Arnsten, lead author and neurobiology professor at Yale.

The brain’s prefrontal cortex (PFC) normally is responsible for so-called executive functions. The ability of the PFC to maintain such memory-based functions declines with normal aging, is weakened in people with ADHD, and is severely disrupted in disorders such as schizophrenia and bipolar disorder.

The current study found that brain cells in PFC contain ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN) that reside on dendritic spines, the tiny protrusions on neurons that are specialized for receiving information. These channels can open when they are exposed to cAMP (cyclic adenosine monophosphate). When open, the information can no longer flow into the cell, and thus the network is effectively disconnected. Arnsten said inhibiting cAMP closes the channels and allows the network to reconnect.

The study also found alpha-2A adrenergic receptors near the channels that inhibit the production of cAMP and allow the information to pass through into the cell, connecting the network. These receptors are stimulated by a natural brain chemical norepinephrine or by medications like guanfacine.

“Guanfacine can strengthen the connectivity of these networks by keeping these channels closed, thus improving working memory and reducing distractibility,” she said. “This is the first time we have observed the mechanism of action of a psychotropic medication in such depth, at the level of ion channels.”

Arnsten said the excessive opening of HCN channels might underlie many lapses in higher cognitive function. Stress, for example, appears to flood PFC neurons with cAMP, which opens HCN channels, temporarily disconnects networks, and impairs higher cognitive abilities.

There is also evidence that this pathway may not be properly regulated with advancing age, resulting in destruction of cAMP. The dysregulation of the pathway may contribute to increased forgetfulness and susceptibility to distraction as we grow older.

The research is also relevant to common disorders such as ADHD, which is associated with weaker regulation of attention and behavior. ADHD is highly heritable, and some patients with ADHD may have genetic changes in molecules that weaken the production of norepinephrine. Treatments for ADHD all enhance stimulation of the norepinephrine receptors.

These new data also have important implications for the researchers’ studies of more severe mental illnesses like schizophrenia and bipolar disorder, which can involve mutations of a molecule called DISC1 (Disrupted in Schizophrenia) that normally regulates cAMP. Loss of function of DISC1 in patients with schizophrenia or bipolar disorder would increase vulnerability to cortical network disconnection and profound PFC deficits. This may be especially problematic during exposure to even mild stress, which may explain the frequent worsening of symptoms following exposure to stress. “We find it remarkable to relate a genetic mutation in patients to the regulation by an ion channel of PFC neuronal networks,” said Arnsten.

Co-authors include Min Wang, Br ian Ramos, Yousheng Shu, Arthur Simen, Alvaro Duqye, Avis Brennan, Susheel Vijayraghavan, Anne Dudley, Eric Nou, David McCormick, James Mazer and Constantinos Paspalas, who also has an appointment at the University of Crete School of Medicine in Heraklion, Greece.

The work was supported by research grants from the National Institute on Aging and the National Institute of Mental Health, as well as from Shire Pharmaceuticals Group plc and an award from the Kavli Institute of Neuroscience at Yale.

Arnsten and Yale have a license agreement with Shire Pharmaceuticals for the development of guanfacine for the treatment of patients with ADHD. Yale has submitted a patent application on the use of HCN blockers for the treatment of PFC cognitive deficits based on the data reported in the Cell paper.

Source - Cell 129: 1-14 (April 20, 2007)Dr. SS/V

Related medicine news :

1. Light therapy decreases depression during pregnancy
2. Light therapy devotes new hope in advanced lung cancer
3. Reducing TB With Ultraviolet Light
4. Exposure To Night Light may Increase The Risk Of Leukemia
5. Improving Lighting Could Bring About A Change In Alzheimers Patients
6. Light Cigarettes - Not So Light?
7. Fungal Infections Effectively Controlled By Light Therapy
8. Light can help fight gum bacteria
9. Lights can lighten your moods
10. Night Light Found To Increase The Risk Of Leukemia
11. UV- Light Tanning As A Type Of Substance-Related Disorder
Post Your Comments:

(Date:11/30/2015)... Los Angeles, CA (PRWEB) , ... November 30, 2015 , ... ... music star Jessie James Decker made a brave but slightly unusual choice to show ... quickly returning to her pre-pregnancy form may have been pre-mature. Saying that she didn’t ...
(Date:11/30/2015)... ... November 30, 2015 , ... ... education course in Dallas, TX, on January 29 and 30, 2016. The course ... the functions of their practices, to learn how to better succeed in the ...
(Date:11/30/2015)... ... November 30, 2015 , ... RoamRight, a leading provider of travel insurance ... Television’s Travel With Kids to promote family vacations around the world. The television ... international destinations and educate families about the people and places of the world, all ...
(Date:11/30/2015)... , ... November 30, 2015 , ... ... up by athletic teams looking to maximize recovery through quality sleep. Tim DiFrancesco, ... and consistently get a better night’s sleep. ChiliPad precisely regulates the surface temperature ...
(Date:11/30/2015)... ... November 30, 2015 , ... Using a combination of two blood sugar tests ... adults, according to a new study by researchers at the School of Public Health ... Adults: Using Combinations of Blood Glucose Tests ,” published in Frontiers in Public Health, ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... , November 30, 2015 /PRNewswire/ ... --> adds a ... for 2010 - 2015 with comprehensive ... a range of deal types, such ... strategic alliances. ...
(Date:11/30/2015)... Diagnostics, the U.S.-based manufacturer of point-of-care biometric testing devices ... systems, and PTS Detect™ cotinine systems, has announced the ... the company into the mHealth market. ... The technology is a system that interfaces with mobile ... and uses test strip technology already developed by PTS ...
(Date:11/30/2015)... , Nov. 30, 2015 iCAD, Inc. ... will feature its latest solutions for advanced image ... of cancer at the Radiological Society of North ... Chicago from November 29 to December ... advances including iReveal®, an automated breast density assessment ...
Breaking Medicine Technology: