Sci. Aging Knowl. Environ., 10 November 2004
Out of Whack, Out of Mind
Misaligned brain cells might sap memory as we age
Your kindergarten teacher was right--neatness counts, even in the brain. Cells that slip out of alignment with age might undermine memory, according to a new study of monkeys. The work could explain the nagging question of why recall falters as we grow older even though we don't normally lose brain cells.
Age might bring wisdom, but it also brings forgetfulness, slower thinking, and waning attention (see "All in Your Mind"). Why time steals our faculties remains a mystery. Researchers long assumed that cells in the brain gradually die as we grow older. However, censuses of neurons toppled that notion, showing no massive cell loss over the years in healthy people. So researchers have sought subtler changes in the structure or arrangement of brain cells that might explain why memory declines. Neurons in many parts of the brain arrange themselves in stacks, known as microcolumns. The cells in these structures appear to work as a unit: They often respond to the same stimuli, for example. Moreover, microcolumns warp in illnesses that decimate memory, such as Alzheimer's disease. Cruz and colleagues wanted to determine whether age distorts the cell stacks.
The researchers first put young and old rhesus monkeys through a set of learning and memory tests. Then they killed the animals and sliced into thin sections a region of the brain that controls capacities such as the temporary storage of information needed to perform a task in progress. To measure the microcolumns, the researchers borrowed a statistical technique from condensed-matter physics that allowed them to map cell coordinates in the slices. For each microcolumn, the scientists calculated the stack's width and its cohesiveness, a parameter known as strength. Although width didn't alter with age, microcolumn strength plunged. That result suggests that cells are slipping out of place over time. Mathematical models of the cell pillars revealed that stack strength diminished with minuscule alterations in the cells' position, bolstering the conclusion. The team also documented that the weaker the columns, the worse the animals' recall. Cells in the columns might be losing the extensions that allow them to receive messages from other neurons, says co-author Douglas Rosene of Boston University. These changes, which might impede memory, could bump the cells out of alignment.
The idea that "minute structural shifts can have severe consequences is very exciting," says neuroscientist Naftali Raz of Wayne State University in Detroit, Michigan. The brain is dynamic, he says, continually making new connections and breaking old ones. But in older brains, we might be seeing the "dark side of plasticity" because cells in more pliable regions, such as the one the authors studied, could be more likely to stray from their proper positions. The work raises the question of when these changes begin, says neuroscientist Jeri Janowsky of Oregon Health and Sciences University in Portland. Studying middle-aged animals could help determine whether the decline is gradual or abrupt. That work might tell us when the brain starts to ignore those lessons from youth.
November 10, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150