| neuroTranSmiTTerS | opinion
Diseases associated with ageing While changes in neurotransmitter function have been difficult to link directly with the outward manifestations of ageing, the role of neurotransmitters in diseases associated with ageing is better understood. one of the most studied diseases in this
respect is alzheimer’s disease, a condition that usually begins after the age of 60 (although it can occur much earlier). it is characterised by gradually advancing dementia as well as pathologic changes in the brain such as a loss of the neurons that give rise to the cortical cholinergic innervation, the appearance of neurofibrillary tangles, comprising paired helical filaments, in the affected areas, together with the presence of amyloid (protein) plaques. There also appears to be a loss of
nicotinic (but not muscarinic) receptors. neurochemically, the most significant change is a decrease in the activity of choline acetyltransferase in all areas of the cortex, which leads to the widespread cholinergic deficit mentioned earlier. There is a correlation between the severity of symptoms and the extent of the deficit. However, treatments that are targeted at reversing the deficit, such as cholinesterase inhibitors, have proven to be of only modest benefit, and the search for a really effective treatment continues. of course, a further implication of the
previous statement is that alzheimer’s disease is probably not simply a disorder of the cholinergic system. in fact, there is ample evidence that serotonergic systems are also involved in alzheimer’s. Post mortem studies have shown a reduced level of serotonin and its metabolites in the brains of alzheimer’s patients, and in some parts of the brain the concentration of serotonin uptake sites appears to be reduced, probably as a result of a reduction in the number of serotonergic nerve terminals. in addition, there is also evidence that
the level of serotonin receptors in the cortex is reduced, especially the type 2a receptor. These particular receptors seem to be associated with cholinergic nerve terminals, pointing to a complex relationship between the two systems. Furthermore, the raphé nuclei, which it will be remembered are the site of greatest serotonin concentration, are one of the areas of the brain where neurofibrillary tangles are most likely to be found. after alzheimer’s disease, the most common neurodegenerative disease
prime-journal.com | March 2011
affecting older people is Parkinson’s disease, and it too is linked to changes in neurotransmitter systems. The most characteristic pathological feature of Parkinson’s
is
neurodegeneration in the substantia nigra (part of the dopaminergic
system
which, as we have seen, undergoes age- related changes), and of the locus coeruleus. at the same time there is a decrease in the concentration of dopamine in the basal ganglia, a fact discovered as long ago as the late 1950s and which led to the use of l-DoPa in the treatment of the condition. most of the clinical features of Parkinson’s
disease can be laid at the door of decreased levels of dopamine in the brain: dopamine receptors, on the other hand, remain largely unaffected. But although therapeutic correction of the dopamine deficit with l-DoPa has had more clinical success than the cholinesterase inhibitors in alzheimer’s disease, it is not ideal as its efficacy declines with time. This has led to other drugs that stimulate dopamine receptors being used, such as the ergot derivative, bromocriptine. as well as the treatment of medical
conditions, the role of neurotransmitters in so many brain functions means that products that affect transmitter function have found a place in the treatment of a variety of conditions in the so-called
neurotransmitter research has been at the
heart of the development of products to treat seemingly myriad diseases, both in the mainstream medical and in the alternative sectors.
‘alternative sector’. The use of tryptophan supplements in the management of sleep disorders has already been mentioned, and the amino acid has also been used to treat ‘jet lag’ (on the grounds that it is a precursor of melatonin). But there are many other examples: the
broad bean Vicia faba, for example, is a rich source of DoPa and is used non- medically to treat conditions thought to be related to disturbances of dopaminergic systems, such as depressed mood and attention disorders. Supplements that modulate the formation of catecholamines are used to treat states in which there is some degree of hyperexcitation, such as anxiety or panic. and supplements designed to increase GaBa levels are used to treat ‘over-stimulation’. neurotransmitter research has been at
the heart of the development of products to treat seemingly myriad diseases, both in the mainstream medical and in the alternative sectors. although the place of the older, well understood transmitters in neuroscience firmly established, the number of new transmitters being discovered means that this area is fertile for the continued emergence of new therapies in the future.
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