From: LARRY KLAES (ljk4_at_msn.com)
Date: Thu Jul 01 2004 - 17:57:05 PDT
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From: cunews_at_cornell.edu<mailto:cunews_at_cornell.edu>
To: CUNEWS-LIFE_SCIENCE-L_at_cornell.edu<mailto:CUNEWS-LIFE_SCIENCE-L_at_cornell.edu> ; CUNEWS-HEALTH-L_at_cornell.edu<mailto:CUNEWS-HEALTH-L_at_cornell.edu> ; CUNEWS-SCIENCE-L_at_cornell.edu<mailto:CUNEWS-SCIENCE-L_at_cornell.edu>
Sent: Thursday, July 01, 2004 5:13 PM
Subject: Cornell News: Astrocytes in brain metabolism
Laser microscopy technique settles long debate about brain chemistry,
could aid studies of Alzheimer's and stroke damage, Cornell
biophysicists report
EMBARGOED UNTIL THURSDAY, JULY 1, 2004, 2 P.M., EST
Contact: Roger Segelken
Office: 607-255-9736
E-mail: hrs2_at_cornell.edu<mailto:hrs2_at_cornell.edu>
ITHACA, N.Y. -- A laser-based microscopy technique may have settled a
long-standing debate among neuroscientists about how brain cells
process energy -- while explaining what's really happening in PET
(positron emission tomography) imaging and offering a better way to
observe the damage that strokes and neurodegenerative diseases, such
as Alzheimer's, wreak on brain cells.
Multi-photon microscopy scans by Cornell University biophysicists of
living brain tissue, as reported in the latest issue of Science (July
2, 2004), reveal exactly how and when neurons (the cells that do the
thinking) and astrocytes (the starburst-shaped glial cells that
service neurons) interact to burn oxygen and glucose, after
astrocytes make lactate from glucose in the bloodstream, to meet the
extraordinary energy demands of the brain.
Based on imaging of two different energy states of NADH (nicotinamide
adenine dinucleotide, a coenzyme involved in brain-cell metabolism),
the Cornell biophysicists say they have both confirmed and redefined
the controversial "astrocyte-neuron lactate shuttle" hypothesis for
brain energy metabolism.
"Over the past decade scientists have passionately debated whether
the activated brain burns glucose completely to water or incompletely
to lactate," said Karl A. Kasischke, M.D., lead author of the Science
paper titled "Neural Activity Triggers Neuronal Oxidative Metabolism
Followed by Astrocytic Glycolysis." "Our results unify existing
contradictory opinions and should be a win-win situation for both
factions," said Kasischke, who is a research associate in the
Developmental Resource for Biophysical Imaging and Opto-electronics
(DRBIO) laboratory headed by Watt W. Webb. Webb, Cornell's S.B.
Eckert Professor in Engineering and a co-inventor of multiphoton
microscopy who also is an author on the Science paper, explains:
"Multiphoton microscopy imaging of intrinsic fluorescence in NADH
shows that early oxidative metabolism in neurons is eventually
sustained -- after about 10 seconds -- by late activation of the
astrocyte-neuron lactate shuttle. Neurons, even at rest, are always
burning glucose and they continue to do so when a signal begins to
pass through the neurons. Then the astrocytes 'kick in' to provide
lactate fuel that they have converted from glucose."
If that seems like a fine point, it is one that escaped scientists
who developed PET and fMRI (functional magnetic resonance imaging)
scanning technologies, as well as the medical personnel who use those
diagnostic tools everyday without knowing exactly what the images
represent. PET and fMRI are not recording neural activity directly,
but rather surrogates for activity -- changes in blood flow (in the
case of PET) and blood oxygenation (fMRI) -- Kasischke explained. He
compares PET and fMRI scans to pictures from cameras with slow
shutter speeds and wide-angle lenses, producing a broad view over a
relatively lengthy time span. A very different picture emerges from
multiphoton microscopy, which can record millisecond changes in
microscopic detail. The ultra-fast microscopic technique can image
individual nerve cells and even their finest extensions, where
important steps in brain-cell metabolism take place.
Multiphoton microscopy is a patented technology that produces
high-resolution, three-dimensional images of tissues -- in the
central nervous system, for example -- with minimal damage to living
cells. The procedure begins when extremely short, intense pulses of
laser light are directed at cells below the surface. The rapid-fire
nature of multiphoton microscopy increases the probability that two
or three photons will interact with individual biological molecules
at the same time, combining their energies. The cumulative effect is
the equivalent of delivering one photon with twice the energy (half
the wavelength, in the case of two-photon excitation) or three times
the energy (one-third the wavelength in three-photon excitation) to
illuminate the smallest details. As a scanning laser microscope moves
the focused beam of pulsed photons across a sample at a precise depth
(plane of focus); cells above or below the plane are not affected.
When repeated scans at different focal planes are "stacked" by
computer processing, a brilliant, three-dimensional picture emerges.
And when a series of scans are "pasted" together, a movie of
split-second changes at the cellular or subcellular level results.
Kasischke has been using multiphoton microscopy to observe brain cell
death as it happens in strokes, a process he has helped illuminate
over the past 10 years. Webb expects the technology to reveal more
about malfunctioning brain cells in neurodegenerative diseases, such
as Alzheimer's and Parkinson's, now that the chemical nature of brain
metabolism is better understood. Other collaborators in the study
are Harshad D. Vishwasrao and Warren R. Zipfel, senior research
associates in Cornell's School of Applied and Engineering Physics;
and Patricia J. Fisher, senior research associate in biomedical
sciences at Cornell's College of Veterinary Medicine. The experiments
and analysis were funded, in part, by grants from Deutsche
Forschungsgemeinschaft (the German Research Foundation) and the U.S.
National Institutes of Health.
-30-
The web version of this release, with accompanying photos, may be
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http://www.news.cornell.edu/releases/June04/astrocyte_neuron.hrs.html
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