Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery of pathway in learning impairment caused by liver disease may lead to drug treatment

20.01.2005


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."

David Greenberg | EurekAlert!
Further information:
http://www.interscience.wiley.com/journal/hepatology
http://www.wiley.com

More articles from Health and Medicine:

nachricht Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)

nachricht Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Better model of water under extreme conditions could aid understanding of Earth's mantle

21.06.2018 | Earth Sciences

What are the effects of coral reef marine protected areas?

21.06.2018 | Life Sciences

The Janus head of the South Asian monsoon

21.06.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>