Sci. Aging Knowl. Environ., 20 August 2003
Neurons grow less flexible with age
Key Words: confocal microscopy bouton dendritic process presynaptic terminal
By middle age, it's easy to be set in our ways. After all, we've long since made up our minds about Brussels sprouts and which side of the bed we prefer. A similar decline in flexibility occurs in particular neurons, according to a study of mice. If the results hold true for nerve cells in general, they could explain how the brain lays down memories and why learning becomes more difficult as we reach our 40s and 50s.
The nervous system of a young animal is in flux, with neurons linking up and separating promiscuously. However, that adaptability wanes throughout adult life. Researchers don't know why, but one possibility is that synapses, the junctions between nerve cells, become more stable with age. Backing the notion, two papers found few changes in nerve-muscle connections after maturity. However, a pair of recent studies on brain pliability have muddied the issue. Both measured the stability of dendrites, the antennae that protrude from neurons and form synapses with other nerve cells, but they found opposite trends in adult rodents.
Taking a step toward resolving the conflict, neurobiologist Jeff Lichtman of Washington University in St. Louis, Missouri, and colleagues focused on a simpler system than the hard-to-study brain, with its jungle of neurons: the submandibular ganglion, a knot of neurons in the neck that amplifies brain messages directed to the salivary glands. Exposing the ganglion requires only simple surgery, so the researchers could observe individual neurons over time and track the position of synapses. To highlight the cells, the team used mice engineered to make a fluorescent yellow pigment in their neurons. The researchers found that a neuron's branching pattern changed less and less with age. For instance, in 6-week-old mice, more than 30% of synapses changed position within a month. In year-old rodents, which are scurrying into middle age, about 20% of the synapses shifted in the same amount of time. Cells in the ganglion are specialized, but brain neurons might respond similarly, says Lichtman.
The work is significant because it cracks one of the fundamental questions of neurobiology--how changeable circuits in the nervous system are--says cell biologist Tobias Bonhoeffer of the Max Planck Institute of Neurobiology in Martinsried, Germany. The results bolster the idea that declining neural flexibility stems from greater synapse stability, he says, and provide a possible mechanism for why learning becomes tougher in middle age. We shouldn't necessarily mourn the loss of youthful versatility, says Lichtman. Children need to absorb information rapidly because they know so little about the world. For seasoned adults, holding on to important experiences might be more important.
Still unresolved is how neurons change in geriatric animals and whether the alterations might underlie the mental declines of old age, says neurobiologist David Riddle of Wake Forest University School of Medicine in Winston-Salem, North Carolina. Despite the general increase in neuron stodginess over time, Lichtman's team observed malleability in mice ready for the rodent retirement home, which suggests that the nervous system can respond to new experiences even in old age. So go ahead, try those Brussels sprouts in chocolate sauce. You might be surprised.
August 20, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150