Sci. Aging Knowl. Environ., 26 November 2003
Vol. 2003, Issue 47, p. nw161
[DOI: 10.1126/sageke.2003.47.nw161]


Eat Less, Nurture Neurons

Cutting calories curbs production of brain-disabling protein as well as Alzheimer's plaques

R. John Davenport

Key Words: RNAi • presenilin • {beta}-amyloid precursor protein • glial fibrillary acidic protein

NEW ORLEANS, LOUISIANA--A diet that extends life also repels brain plaques associated with Alzheimer's disease (AD), according to research presented here 10 November 2003 at the Society for Neuroscience Annual Meeting. The feeding plan also reduces amounts of a brain protein that apparently impairs the ability of neurons to make new connections.

Calorie restriction (CR)--slashing food intake by about one-third--extends the life span of numerous creatures, including rodents (see Masoro Review). The meager diet staves off age-related diseases such as diabetes and cancer, and some studies suggest that it also helps neurons from old animals maintain their youthful vitality. To investigate whether CR thwarts AD, neurobiologist Todd Morgan of the University of Southern California in Los Angeles and colleagues fed stingy meals to two lines of mice that had been genetically altered to accumulate {beta}-amyloid plaques. These protein clumps riddle the brains of Alzheimer's patients and exacerbate or cause dementia (see "Detangling Alzheimer's Disease"). After several weeks of reduced-calorie dining, the mice showed a 40% to 55% decrease in the number of plaques compared with well-fed animals. Further analysis of one of the mouse lines revealed that the plaques were smaller than those in control rodents.

Additional experiments suggest that CR might preserve brainpower by blunting the production of a protein that becomes more abundant with age. Animals from both lines carried less of the protein--called GFAP--when they dieted. GFAP shows up predominantly in astrocytes, brain cells that intertwine with neurons and help them grow. After an injury, astrocytes change their tune, depositing scar tissue and blocking neuron growth; the cells ramp up GFAP production when they're in this activated state.

In a second presentation, the researchers described experiments that probed whether a dearth of GFAP hinders astrocytes from breathing life into neurons. They collected astrocytes from young and old mice, grew them in culture, and layered embryonic neurons on top. Young astrocytes carried little GFAP and encouraged the growth of more branchlike structures on neurons than did old astrocytes, which harbor much more of the protein. These extensions help neurons connect with each other, fostering memory storage and allowing the brain to recover from injury. Next, the scientists tested whether GFAP thwarted formation of the extensions. Blocking GFAP production in old astrocytes prompted new branches to form, and permanently cranking up the protein in young astrocytes curtailed sprouting. Together, the results suggest that the age-related rise in GFAP concentration undermines neurons' resilience.

No one had shown that CR diminishes plaque burden, says neuroscientist Mark Mattson of the National Institute on Aging in Baltimore, Maryland. The work meshes with previous studies hinting that CR protects neurons, and it suggests a possible mechanism through which CR preserves brain operations, he says. How GFAP cripples neurons isn't clear, he adds. It might constitute part of a signal that blocks neuron growth, or large amounts of it might make astrocytes sick. Resolving such issues could help researchers understand how to keep brains sparkling clean with age.

--R. John Davenport

November 26, 2003
  1. N. V. Patel et al., Caloric restriction reduces amyloid plaque number and size in two transgenic models of Alzheimer disease. Society for Neuroscience Annual Meeting, 8-12 November 2003, New Orleans, Louisiana. [Meeting Web site]
  2. M. Wei, T. E. Morgan, C. E. Finch, I. Rozovsky, Neuronal sprouting is impaired in cocultures with old astrocytes: Potential role of age-related increase of GFAP. Society for Neuroscience Annual Meeting, 8-12 November 2003, New Orleans, Louisiana. [Meeting Web site]
Citation: R. J. Davenport, Eat Less, Nurture Neurons. Sci. Aging Knowl. Environ. 2003 (47), nw161 (2003).

Science of Aging Knowledge Environment. ISSN 1539-6150