opinion | neuroTranSmiTTerS | obesity, as well as
hallucinogenic drugs. For many years, amino
acids were not recognised as neurotransmitters because they are ubiquitous cellular components, and the enzymes involved in their formation are not specific to nerve cells (unlike the case with the neuro- transmitters already mentioned). The majority of amino acid neurotransmitters are also involved in protein synthesis, the exception being GaBa. in nerve cells, glutamate is
formed within the mitochondria, then transported to the cytoplasm and stored in synaptic vesicles until needed. after release, its actions are terminated by a high-affinity reuptake system into the presynaptic nerve ending. The processes that handle GaBa in nerve cells are similar, except that its reuptake is rather more complicated: it is first converted to glutamate and then to glutamine, which re-enters the nerve cell. There it is converted back to GaBa. There are at least three different types
of glutamate receptor. Two are linked to ion channels, while the third is a G-protein coupled receptor, which means it directly modulates intracellular signalling. opening ion channels drives the cell towards depolarisation; in other words, glutamate has an excitatory action. Postsynaptic GaBa receptors are also ionotropic but in this case their stimulation results in hyperpolarisation.
Age-related changes There is abundant evidence that the process of normal ageing is associated with a number of changes to the neurotransmitters and synaptic transmission in the brain. a couple of general points should be made. First, although each of the steps involved in neurotransmitter synthesis, function and degradation may be altered in some neurons, it is not the case that all neurons of a particular type are affected, or even all the neurons in a particular part of the brain. Second, a decline in the function of a particular neurotransmitter system does not necessarily imply a loss of physiological function.
60 ❚ March 2011 |
prime-journal.com Furthermore, it is important to
differentiate between changes in neurotransmitter systems that occur as part of the normal ageing process, and changes that occur in connection with particular pathological conditions associated with old age, such as alzheimer’s disease or Parkinson’s disease. While these conditions were once regarded as an exaggerated version of old age, it is now thought
that the
p a t holo g i ca l changes that occur in the brains of
patients go beyond the normal
ageing process. as described above, most neurotransmitters
systems
share a number of basic processes in common – biosynthesis of
the
transmitter, its storage in the presynaptic terminal, its release in response to a nervous impulse,
its
Molecule of the hormone dopamine
interaction with postsynaptic receptors, and its reuptake and/or degradation – and any of these may be affected by the ageing process. For example, the synthesis of acetylcholine has been shown to decrease with age in certain parts of the brain. Similarly, there is a decline in the number of acetylcholine, dopamine and serotonin receptors in several parts of the brain although, interestingly, receptors for some amino acids do not seem to be affected by age in the same way. in the case of
acetylcholine, both pre- and postsynaptic changes occur with age. Presynaptically, the activity of choline acetyltransferase decreases with age, although
the
acetyltransferase activity is decreased, although its actual cause is hotly debated: some investigators have claimed to have seen a decrease in the number or size of cholinergic neurons. Similarly, there is evidence for decreased
dopamine metabolism in some parts of the brain, as well as a decrease in the number of dopamine receptors. Some researchers have claimed that there is also a decrease in the number of dopaminergic cells in brain areas such as the substantia nigra, but the evidence for this is inconclusive. other age-related changes that have been reported include decreased activity by the transport mechanism by which dopamine is taken up from the synapse, and increased levels of monoamine oxidase B, one of the enzymes responsible for the metabolism of dopamine. Concentrations of both serotonin
receptors and the serotonin transporter, meanwhile, have been shown to decrease with age. These observations are based on both measurement of the serotonin- binding capacity of post mortem brain samples and on tracer studies using positron emission tomography (PeT) in living humans.
The best advice for slowing the ageing process remains the
decrease is not uniform throughout the brain. For example, it is typically around 10% in the cerebral cortex, but may be as high as 30% in areas like the hippocampus and the striatum. This decrease cannot be accounted for by neuronal loss, although some loss does undeniably occur in these parts of the brain. Postsynaptically a decrease in the level of the muscarinic receptor has been reported in areas where choline
same: consume a healthy diet, take regular exercise, and keep mentally active.
Amino acids as for amino acids, significant decreases in the level of glutamate decarboxylase, the enzyme that converts glutamate to GaBa, have been found in post mortem brain samples (particularly from the cortex and thalamus), and a decrease in GaBa receptors has been found in aged animal, but not human, brain samples. a loss of GaBa receptors is one of the characteristics of Huntington’s disease. The fact that changes
occur in various neurotransmitter systems during the ageing process has
prompted many practitioners to suggest that measures designed to reverse these changes, such as dietary changes or the use of supplements, might be able to reverse the ageing process, even though no cause-and-effect relationship has been found. The best advice for slowing the ageing process remains the same: consume a healthy diet, take regular exercise, and keep mentally active.
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