Sci. Aging Knowl. Environ., 25 June 2003
Vol. 2003, Issue 25, p. nw90
[DOI: 10.1126/sageke.2003.25.nw90]


You Must Remember This

Experimental compounds curtail age-linked memory loss and prevent brain oxidation in rodents

Mitch Leslie;2003/25/nw90

Key Words: peroxidation • SOD/catalase mimetic

Ah, the golden years--when people forget the names of ordinary household objects and where they parked the car. A new study reveals that two compounds that squelch destructive byproducts of metabolism prevent memory loss in aging mice and shield brain molecules from damage. The findings back a leading hypothesis for the cause of age-related memory declines and suggest that oxidant-quelling drugs might help the elderly retain their remembrance of things past.

Weakening memory is an inevitable consequence of aging (see "All in Your Mind"), but its cause remains uncertain. Many researchers suspect that the brain takes a beating from reactive oxygen species (ROS), molecules released by metabolism that corrode proteins, fats, and DNA (see "The Two Faces of Oxygen"). Although several studies have found increased oxidation damage in the brains of older animals, the connection is circumstantial. Digging deeper, molecular neurobiologist Michel Baudry of the University of Southern California in Los Angeles and colleagues measured the effects on memory of two experimental compounds that sop up oxidants, known as EUK-189 and EUK-207 (see "Drugs Protect Mice From Pernicious Forms of Oxygen").

The researchers used a standard test to gauge recall ability in middle-aged mice. First, they placed each mouse alone in a small cage and gave it an electric shock at the same time a tone played. Later the team either returned the rodent to the test cage or played the tone, then tallied how long it remained immobile--its normal response to fear. The procedure indicates how well the animal learns to associate the tone or isolation cage with the jolt; the longer it's motionless, the better it remembers. For 3 months before these experiments, some mice received low or high doses of EUK-189 or EUK-207. Untreated animals showed a steep decline in memory between the ages of 8 and 11 months. However, the treatment reduced or halted this decay. For example, in their response to the cage, 11-month-old mice that had received low doses of EUK-207 outscored controls of the same age by about 300%; their memory was nearly as perky as the untreated 8-month olds'. The compounds slashed the amount of oxidative damage to proteins and fats in the animals' brains. EUK-207 also shielded nucleic acids in the hippocampus and amygdala, regions vital for memory. The EUK compounds outperformed other antioxidants by rejuvenating brain proteins rather than by just curtailing damage, Baudry notes: Treated 11-month-olds carried fewer oxidative scars than did untreated 8-month-olds.

"The data do support that notion that oxidative damage in the brain is associated with loss of memory," says free radical biologist Robert Floyd of the Oklahoma Medical Research Foundation in Oklahoma City. However, he says that rapid deterioration of memory in the untreated middle-aged mice might not be typical; it could be a quirk of the strain used in the study. Several studies indicate that human recollection starts dwindling in middle age, Baudry counters. The current work suggests that oxidant fighters might curb the decline and help older folks remember where they left the, you know, the whatchamacallit.

--Mitch Leslie; suggested by Greg Liszt

June 25, 2003
  1. R. Liu et al., Reversal of age-related learning deficits and brain oxidative stress in mice with superoxide dismutase/catalase mimetics. Proc. Natl. Acad. Sci. U.S.A., 18 June 2003 [e-pub ahead of print]. [Abstract] [Full Text]
Citation: M. Leslie, You Must Remember This. Sci. SAGE KE 2003, nw90 (25 June 2003);2003/25/nw90

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