Nitric Oxide Can Alter Brain Function

Finding has implications for the treatment of neurodegenerative disease and dementia

LEICESTER, England, Nov. 26,2008--Research from the Medical Research Council (MRC) Toxicology Unit at the University of Leicester shows that nitric oxide (NO) can change the computational ability of the brain. This finding has implications for the treatment of neurodegenerative diseases such as Alzheimer’s Disease and our understanding of brain function more generally.

The research is led by Professor Ian Forsythe and is reported in the journal Neuron on 26th November.

Professor Forsythe, of the MRC Toxicology Unit, explains: “It is well known that nerve cells communicate via the synapse – the site at which chemical messengers (neurotransmitters such as acetylcholine or glutamate) are packaged and then released under tight control to influence their neighbours.

“Nitric oxide is a chemical messenger which cannot be stored and can rapidly diffuse across cell membranes to act at remote sites (in contrast to conventional neurotransmitters which cannot pass across cell membranes).

“It is broadly localized in the central nervous system, where it influences synaptic transmission and contributes to learning and memory mechanisms. However, because it is normally released in such minute quantities and is so labile, it is very difficult to study.

“We have exploited an in vitro preparation of a giant synapse -called the calyx of Held, developed here at the University of Leicester in the 1990s- and its target in the auditory pathway to explore nitric oxide signalling in the brain.

“We show that NO is made in response to incoming synaptic activity (activity generated by sound received by the ear) and that it acts to suppress a key potassium ion-channel (Kv3). Normally these ion-channels keep electrical potentials very short-lived, but nitric oxide shifts their activity, slowing the electrical potentials and reducing information passage along the pathway, acting as a form of gain control.

“Surprisingly, the whole population of neurons were affected, even those neurons which had no active synaptic inputs, so indicating that nitric oxide is a ‘volume transmitter’ passing information between cells without the need for a synapse. Such a function is ideal for tuning neuronal populations to global activity. On the other hand, too much nitric oxide is extremely toxic and will cause death of nerve cells; so within the kernel of this important signaling mechanism are the potential seeds for neurodegeneration, which if left unchecked contribute to the pathologies of stroke and dementias.”

In the future Professor Forsythe’s research group will be trying to understand how these signalling mechanisms are applicable elsewhere in the brain and will investigate how aberrant signalling contributes to neurodegenerative disease processes such as in Alzheimer’s disease..

 

Notes to Editors: For more information on this please contact:

Professor Ian D. Forsythe Toxicity at the Synaptic Interface MRC Toxicology Unit University of Leicester Leicester. LE1 9HN. UK.

email: idf@le.ac.uk

Please cite MRC Toxicology Unit and University of Leicester in any report

 

 

LEICESTER: University of the Year 2008-Times Higher Education Ather Mirza Press and Corporate Communications Division of Marketing and Communications University of Leicester University Road Leicester LE1 7RH tel: 0116 252 3335 email: pressoffice@le.ac.uk

UNIVERSITY OF LEICESTER - A member of the 1994 Group of universities that share a commitment to research excellence, high quality teaching and an outstanding student experience.

* Named University of the Year by Times Higher (2008) Shortlisted (2006, 2005) and by the Sunday Times (2007) * Ranked second to Cambridge for student satisfaction amongst full time students taught at mainstream universities in England * Ranked as a Top 20 university by the Sunday Times, Guardian,Times and UK Complete University Guide, published in The Independent * Ranked in world’s top 200 universities by Shanghai Jiao Tong International Index, 2005-08 and the Times Higher Education-QS World University Rankings * Ranked top 10 in England for research impact by The Guardian * Students’ Union of the Year award 2005, short listed 2006 and 2007 Founded in 1921, the University of Leicester has more than 20,000 students from 136 countries. Teaching in 18 subject areas has been graded Excellent by the Quality Assurance Agency- including 14 successive scores - a consistent run of success matched by just one other UK University. Leicester is world renowned for the invention of DNA Fingerprinting by Professor Sir Alec Jeffreys and houses Europe's biggest academic Space Research Centre. 90% of staff are actively engaged in high quality research and 13 subject areas have been awarded the highest rating of 5* and 5 for research quality, demonstrating excellence at an international level. The University's research grant income places it among the top 20 UK research universities. The University employs over 3,000 people, has an annual turnover of over ??m, covers an estate of 94 hectares and is engaged in a ??m investment programme- among the biggest of any UK university.

 

Ather Mirza Press and Corporate Communications Division of Marketing and Communications University of Leicester University Road Leicester LE1 7RH tel: 0116 252 3335 email: pressoffice@le.ac.uk

UNIVERSITY OF LEICESTER - A member of the 1994 Group of universities that share a commitment to research excellence, high quality teaching and an outstanding student experience.

* Named University of the Year by Times Higher (2008) Shortlisted (2006, 2005) and by the Sunday Times (2007) * Ranked second to Cambridge for student satisfaction amongst full time students taught at mainstream universities in England * Ranked as a Top 20 university by the Sunday Times, Guardian,Times and UK Complete University Guide, published in The Independent * Ranked in world’s top 200 universities by Shanghai Jiao Tong International Index, 2005-08 and the Times Higher Education-QS World University Rankings * Ranked top 10 in England for research impact by The Guardian * Students’ Union of the Year award 2005, short listed 2006 and 2007 Founded in 1921, the University of Leicester has more than 20,000 students from 136 countries. Teaching in 18 subject areas has been graded Excellent by the Quality Assurance Agency- including 14 successive scores - a consistent run of success matched by just one other UK University. Leicester is world renowned for the invention of DNA Fingerprinting by Professor Sir Alec Jeffreys and houses Europe's biggest academic Space Research Centre. 90% of staff are actively engaged in high quality research and 13 subject areas have been awarded the highest rating of 5* and 5 for research quality, demonstrating excellence at an international level. The University's research grant income places it among the top 20 UK research universities. The University employs over 3,000 people, has an annual turnover of over ??m, covers an estate of 94 hectares and is engaged in a ??m investment programme- among the biggest of any UK university.

 

 

Posted: November 2008

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