Sci. Aging Knowl. Environ., 20 August 2003
Mitochondrial exchange makes dumb mice smarter and smart mice dumber
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/sageke;2003/33/nw117
Key Words: Morris water maze radial maze Krushinsky test
It sounds like the rodent version of the movie Freaky Friday, in which a mother and daughter swap bodies. Switching mitochondria--the cell's powerhouses--between two lines of mice flip-flops their ability to learn, according to new work. The study is the first to show that genetic characteristics of mitochondria influence brain function, but the mechanism remains unknown.
Mitochondria convert food into fuel for essential processes, such as thinking and flexing muscles. They carry their own DNA, which encodes proteins that team up with those produced by genes in the nucleus to form power-generating molecular machines. Diseases stemming from mutations in mitochondrial genes frequently lead to dementia and other nervous system defects, and some studies have connected mitochondrial DNA variations to an increased risk of neurodegeneration. However, scientists have not established the role of mitochondrial genes in normal brain function.
To explore that potential role, neurogeneticist Pierre Roubertoux and colleagues at the French National Center for Scientific Research in Marseille exchanged mitochondria between two lines of rodents, called H and N. Mitochondria pass from mother to offspring, so the researchers mated females of one line with males of the other. Further breeding of the progeny produced H animals with N mitochondria and N animals with H mitochondria.
The researchers subjected the two parental lines and the two new, hybrid varieties to learning tests: remembering the location of food in a maze, locating a hidden escape platform in a tub of water, and finding a cup of milk after it was removed from view. Of the two parental lines, H animals performed the tasks faster than did N rodents. Mental abilities of the two hybrid lines shifted toward those of the parental animals. H animals with N mitochondria performed worse than H animals but not as poorly as N animals. And N animals with H mitochondria showed better memory than N animals but did not match wits with H animals. The results suggest that changes to the mitochondrial genome can modify learning. The mitochondrial shuffling also alters aging, the data suggest. Rodents' performance in learning tasks weakens over time. This decline steepened in the H animals with N mitochondria, compared with H parental animals. But it didn't change in N animals with H mitochondria, compared with N parental animals.
The researchers have clearly shown that changing mitochondrial DNA without modifying the nuclear genome alters cognition, says neuroscientist M. Flint Beal of Cornell University's Weill Medical College in New York City; "that's never been demonstrated before." Molecular geneticist Douglas Turnbull of the University of Newcastle upon Tyne, U.K., agrees that it is a solid study, but he wants to see experiments that address how the swap alters physiology. Perhaps variations in mitochondrial genes stifle intellect by attenuating energy production, for instance. Alternatively, the transfers could adjust the activity of nuclear genes that control mental prowess; Roubertoux's team is investigating that possibility. Future studies might clarify whether mitochondria similarly modulate human thinking. If so, we might hope to wake up at the end of the week with Einstein's mitochondria.
--R. John Davenport
August 20, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150