Nitric oxide link to Alzheimer's
Researchers hope their findings that NO can change the computational ability of the brain will improve understanding of brain function
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Thursday, 27, Nov 2008 10:05
A new connection between neurodegenerative diseases such as Alzheimer's and nitric oxide (NO) has been established by UK scientists.
Researchers from the University of Leicester hope their findings that NO can change the computational ability of the brain will improve understanding of brain function.
It was already widely known that nerve cells communicate via the synapse – the site at which chemical messengers are packaged and then released under tight control to influence their neighbours.
NO, found in the central nervous system, is a chemical message that cannot be stored but rapidly diffuses across cell membranes to act at remote cites.
The influence it imposes upon synaptic transmission 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," said Professor Ian Forsythe of the Medical Research Council toxicology unit at the University of Leicester.
"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," Prof Forsythe continued in the journal Neuron.
"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 signalling mechanism are the potential seeds for neuro-degeneration, which if left unchecked contribute to the pathologies of stroke and dementias."