Featured Research

from universities, journals, and other organizations

Discovery Of Pathway In Learning Impairment Caused By Liver Disease May Lead To Drug Treatment

Date:
January 28, 2005
Source:
John Wiley & Sons, Inc.
Summary:
Liver disease sometimes causes hepatic encephalopathy, which involves brain damage, personality changes, and intellectual impairment due to hyperammonemia (high levels of ammonia in the blood). However, the mechanisms involved in both learning and how liver disease leads to learning impairment are unclear.

Liver disease sometimes causes hepatic encephalopathy, which involves brain damage, personality changes, and intellectual impairment due to hyperammonemia (high levels of ammonia in the blood). However, the mechanisms involved in both learning and how liver disease leads to learning impairment are unclear.

In a new study led by Vicente Felipo of the Laboratory of Neurobiology at the Fundacion Valenciana de Investigaciones Biomedicas in Valencia, Spain and published in the February 2005 issue of Hepatology, researchers hypothesized that impaired learning was due to a defect in the glutamate-nitric oxide-cGMP pathway in the brain and that administering sildenafil to increase cGMP would restore learning ability. Sildenafil, commonly known as Viagra, is known to prevent the destruction of cGMP and allow it to accumulate in the body. Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc. is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

Researchers examined four groups of rats in their study: rats in which they constructed portacaval shunts (a treatment used to treat high blood pressure in the liver due to liver disease that is believed to be one of the causes of hepatic encephalopathy, and also a model of chronic liver failure in rats); rats with portacaval shunts that were given sildenafil; rats that were fed an ammonium-containing diet; and rats that were fed the diet and given sildenafil. They also used control groups consisting of rats fed a normal diet both with and without sildenafil. All animals were subjected to a maze learning test four weeks following surgery or from the date when drug treatment began. Levels of both cGMP and ammonia in brain were measured using a microdialysis probe.

Results showed that while rats with the portacaval shunt showed a reduced learning ability, treatment of shunted rats with sildenafil restored their ability to learn. Tests showed that the concentration of cGMP was reduced in the extracellular fluid in brains of shunted rats compared with controls and that treatment with sildenafil restored levels of cGMP in these animals. In addition, further tests showed a reduction of 74 percent in the function of the glutamate-nitric oxide-cGMP pathway in shunted rats, while treatment with sildenafil significantly enhanced the function of this pathway. These evaluations were also performed on rats with hyperammonemia. Results showed that chronic hyperammonemia significantly reduced the rats' ability to learn, but that treatment with sildenafil restored their learning ability. While sildenafil treatment restored levels of cGMP and enhanced the function of the glutamate-nitric oxide-cGMP pathway in hyperammonemic rats, it did not affect ammonia levels.

"The fact that rats with portacaval anastomosis [shunts] or with hyperammonemia without liver failure show the same alterations in the function of the [glutamate-nitric oxide-cGMP] pathway, extracellular cGMP and learning ability indicates that hyperammonemia, which is the only common alteration in both models, is responsible for the alteration of the function of the pathway and, subsequently, of the impairment of learning ability," the authors state. They note, however, that an excessive increase in cGMP may impair learning and that it must be kept high but below a certain threshold to reach maximum learning ability.

The authors conclude: "Although caution must be taken considering the possible deleterious increase in the existing vasodilatation in liver disease by sildenafil, pharmacological manipulation of cGMP in brain by safe procedures may be a useful treatment to restore cognitive and intellectual functions in patients with overt or minimal hepatic encephalopathy."

###

Article: "Oral Administration of Sildenafil Restores Learning Ability in Rats with Hyperammonemia and with Portacaval Shunts," Slaven Erceg, Pilar Monfort, Mariluz Hernαndez-Viadel, Regina Rodrigo, Carmina Montoliu, Vicente Felipo, Hepatology; February 2005; 41:2.


Story Source:

The above story is based on materials provided by John Wiley & Sons, Inc.. Note: Materials may be edited for content and length.


Cite This Page:

John Wiley & Sons, Inc.. "Discovery Of Pathway In Learning Impairment Caused By Liver Disease May Lead To Drug Treatment." ScienceDaily. ScienceDaily, 28 January 2005. <www.sciencedaily.com/releases/2005/01/050124003559.htm>.
John Wiley & Sons, Inc.. (2005, January 28). Discovery Of Pathway In Learning Impairment Caused By Liver Disease May Lead To Drug Treatment. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2005/01/050124003559.htm
John Wiley & Sons, Inc.. "Discovery Of Pathway In Learning Impairment Caused By Liver Disease May Lead To Drug Treatment." ScienceDaily. www.sciencedaily.com/releases/2005/01/050124003559.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) — Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) — Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) — A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) — The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins