Wednesday, February 27, 2013

In new bodies, brain cells find longer lives

Transplanted mouse neurons survive for twice the lifespan of a mouse.

The search for the fountain of youth is nothing new; we humans have long been trying to lengthen our lifespans. In recent years, science and medicine have made great strides in increasing how long we live. The average life expectancy of an American is now more than 78 years, up nearly a decade since 1960. But as we live longer and longer, what will happen to the cells that compose our brains?  If we are able to live to 120, 150, or longer, can our brain cells survive that long too? Or in the future, will our neurons die long before we do, leaving our brains depleted?
To start answering this question, three Italian researchers carried out a series of transplant experiments and found that neurons can last far longer than the organisms in which they originated. In this week’s issue of PNAS, the scientists describe their research, which suggests neuron survival may be more flexible than previously thought.
The researchers chose to work with mice and rats. The two animals are similar in many regards, but they differ substantially in their life expectancy (rats survive far longer than mice). By transplanting cells between these two species, the scientists could determine whether neurons have a pre-programmed lifespan based on genetics or whether they have more plasticity.
They took “neuroglial precursors”—cells that develop into neurons—from mice bred to express a fluorescent protein and then transplanted these cells into rat embryos. Thanks to the fluorescence, the researchers could visibly track the transplanted neurons as the rats aged, keeping an eye on the cells' development, status, and survival.
The researchers focused on a certain type of neuron, called a Purkinje cell, that plays a role in motor function and movement. These large neurons tend to deteriorate and die off as animals age. Mice, for instance, lose as many as 40 percent of their Purkinje cells by the time they die.
The mouse-donated cells took hold in 20 of the 59 rats, developing in these animals just as normal rat neurons would. However, they retained many of the characteristics of mouse neurons, such as shape and size. Just as they would have under normal circumstances, the transplanted brain cells deteriorated somewhat, slowly losing dendritic spines.
But inside the rats’ brains, the cells didn’t die off after 18 months, when most of the mice they originated in would have died. Instead, the neurons survived as long as the host rats did, up to 36 months. In other words, inside a rat’s brain, the donated neurons survived for the lifespan of two average mice.
This discovery suggests brain cell survival isn’t pre-programmed by genetics—or at least it isn’t completely tied to the lifespan of the organism where the cells originate. Instead, their survival may depend on the microenvironment of the organism that they inhabit. Neuron aging and survival appear to be controlled by two processes which—while related—may be separable. But there's much more to learn, since we don't yet know much about either of these processes.
Despite the unknowns, this is good news for those of us who want to live long past 78 years (and still be coherent enough to enjoy it). The research suggests that scientists could potentially extend our lifespans dramatically without leaving us devoid of brain cells.
PNAS, 2013. DOI: 10.1073/pnas.1217505110  (About DOIs).
Listing image by Hey Paul Studios

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