Neurotransmitters

The idea that nerve cells function as independent units and form a physical contact to facilitate intercellular communication was first proposed by neurobiologists at the turn of the twentieth century. This concept, termed the neuron theory of brain function, is based on the knowledge that the nervous system is not made up of a contiguous labyrinth of intertwining processes but instead represents a collection of neurons, together with their axons and dendrites, that form close functional contacts to permit the transfer of information from one cell to another. The site at which the contact between two neurons is made is called the synapse; and the chemical signal that is used for mediating communication between neurons is the neurotransmitter.

For both the central and peripheral nervous system there are a relatively small number of molecules that fulfill the criteria of a neurotransmitter. These include dopamine (DA), norepinephrine (NE), epinephrine, serotonin, histamine, acetylcholine (Ach), gamma-amino butyric acid (GABA), glycine, and glutamate. During development the nervous system takes on the responsibility for controlling a variety of body functions including movement, consciousness, learning and memory, and sensory processing. A fully competent nervous system is essential for maintaining the integrity of body functions in adulthood while an aging nervous system has often been coupled with an irreversible loss of global function. However, this oversimplified picture of brain aging is far from the truth. Research conducted since the early 1980s has indicated that an age-related decline in neurotransmitter function is not a global phenomenon. Instead, studies have reported that just as organisms age at different rates, so do the different neurotransmitter systems in their bodies; and that wide differences in neurotransmitter levels exist in the brain between individuals of like age. This divergence between biological and chronological old age is most obvious in the human population but is also found in aged rodents and nonhuman primates. Functional variability with age is tied closely to the variability in the biochemical and anatomical changes found in different neurotransmitter systems of the brain and is unquestionably linked to genetic and environmental factors that influence the "rate" at which we age. Thus, the degree to which age-related anatomical and biochemical changes occur in neurotransmitter systems of the brain can be described as variable at best.

When investigating age-related alterations in neurotransmitter function it is important to realize that a decline of a particular neurotransmitter does not always equate with a loss in physiological function. Previous studies have reported that age-related changes in the brain cannot be represented by simple cell loss that leads to functional decline. Rather, it is understood that the aging brain represents a composite of various adaptive and compensatory responses, which work together to maintain and repair the brain's neural networks in response to naturally occurring cell loss or neurochemical deficits that are brain region, cell type, and species specific. In addition, it is important to distinguish between changes in neurotransmitter systems that are seen in normal aging with that characteristic of the diseased state. While it was once believed that neurodegenerative diseases such as Alzheimer's and Parkinson's disease were part of an accelerated aging process it is now known that the neuropathology of the diseased brain represents extensive neuronal degeneration and cell death that goes beyond normal aging. In fact anatomical studies with sophisticated neuronal counting techniques indicate that the degree of neuron loss in the aged brain is quite low and age-related changes ascribed to neurotransmitter neurons may not affect our activities of daily living until we are well into our late seventies or eighties.

If global neurodegeneration and cell death are not characteristic of neurotransmitter neurons then what are the changes seen in neurotransmitter neurons with increased age? To answer this question we must consider that changes can occur in either the presynaptic or postsynaptic components involved in information transfer. Age-related changes in the presynaptic components can include changes in neurotransmitter synthesis, storage, synaptic release, and neurotransmitter re-uptake. Changes in postsynaptic components include changes in neurotransmitter receptors (protein complexes that bind neurotransmitters), secondary messenger systems (responsible for transfer of information into neurons), and enzymes involved in neurotransmitter degradation. The following is a brief overview of the age-related changes that have been described for the four most common neurotransmitters found in the central and peripheral nervous system.