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Brain - Modifying Changes In The Aging Nervous System

age physiological clinical neural neurons age growth

Neural plasticity is a term that describes the ability of synapses, dendrites, axons, and other aspects of neurons to change—usually in an adaptive fashion. Plasticity is very potent in developing organisms, and it is now established that older brains retain much capacity for change as well. Research has shown that new synapses can form in older brains in response to injury or environmental manipulations, and that dendrites continue to be modifiable. However, the process generally takes longer and may not reach the magnitude typical of younger brains. The ability of the adult nervous system to engage mechanisms of synaptic plasticity has at least two important implications. First, degenerative tendencies may be counteracted by replacement of damaged synapses and repair of neural circuits. Second, the nervous system can continue to manifest the normal, adaptive types of synaptic plasticity exhibited by young individuals.

The dynamic properties of the older nervous system provide potential opportunities for the development of strategies aimed at modulating the direction or severity of negative age-related changes. A number of approaches are being investigated by researchers. In one way or another, most approaches attempt to enhance neural functioning by promoting the activity of various neurotransmitters or other physiologically important substances that protect neurons from age-related damage or improve neural functioning per se. For example, diets that promote the general health of cardiovascular and other systems are also good for the nervous system.

Neurotrophic factors such as nerve growth factor (NGF) are essential for the maintenance, growth, and survival of neurons both during development and in adults. Administration of neurotrophic factors has been shown to retard or prevent neural degeneration in experimental animals, and infusion of NGF may be able to prevent shrinkage of neurons typically observed with age. It appears that neurotrophic factors may have a variety of potentially beneficial effects on the aging nervous system. Some of these may be harnessed for clinical use.

Calorically restricted diets can extend longevity of rodents, slow certain age-related physiological declines, and decrease tumors and diseases. Although much of this research has focused on non-neural systems, there is ample evidence that dietary restriction modulates aging of the brain. Effects of dietary restriction on some of the general concomitants of neural aging, such as accumulation of lipofuscin ("age pigment") in neurons, the efficacy of glial cells, and loss of dendritic spines, have been reported.

Relatively simple environmental manipulations can have beneficial effects on the brain. Young and old rats living in an "enriched" environment (e.g., ten rats per cage, large space, toys) may exhibit a thicker cerebral cortex, compared to like-aged unenriched rats. Enhancement of dendritic growth and complexity have also been demonstrated in studies of environmental enrichment. Some evidence has linked neurotrophic factors to environmental enrichment and improved cognitive performance. The expression of NGF has been found to increase under these conditions. It could be that enriched environments or behaviors are associated with increased neural activity, which results in an upregulation of nerve growth factors, which in turn leads to enhanced neuronal survival, growth, and plasticity.

Unfortunately, age-related damage to neurons can be too severe to be managed by neurotrophins or environmental manipulations. This is especially true of neurodegenerative diseases. In such cases, transplantation or grafting of new neurons into the damaged site might prove to be feasible approach. The main problems are survival of the graft and, more importantly, appropriate rewiring of circuitry with the host brain. There is a tendency of the grafted tissue to make contacts appropriate for their neurotransmitters and circuits, although this depends on brain region and other variables. The possibility of replacing brain tissue lost to aging—thereby restoring function—is intriguing. Although controversial and inconsistent, improvements have been obtained by grafting tissue from the adrenal gland or fetal substantia nigra into Parkinson's patients. Encouraging results have been obtained from animal research in other brain regions as well, and several studies have shown that fetal brain tissue can be successfully transplanted into the brains of aged rodents. A big issue is whether complex behaviors and cognitive processes of humans might ever benefit from neural grafting. It is one thing to enhance dopamine activity in Parkinson's patients and another to replace intricate neural circuitry underlying cognitive processes. The latter may never be attainable. For now, the utility of neural grafts is likely to be found in their capacity to generate growth factors and other beneficial substances, or boost the activity of certain circuits by replenishing neurotransmitters.



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