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The Journal of Neuroscience, December 15, 1998, 18(24):10366-10374
Effects of Transforming Growth Factor- (Isoforms 1-3) on
Amyloid- Deposition, Inflammation, and Cell Targeting in Organotypic
Hippocampal Slice Cultures
Marni E.
Harris-White1,
Teresa
Chu1,
Zerlinde
Balverde1,
Jason J.
Sigel1,
Kathleen C.
Flanders3, and
Sally A.
Frautschy2
1 Department of Medicine, University of California Los
Angeles and Veterans Affairs Medical Center Sepulveda, Sepulveda,
California 91343, 2 Department of Neurology, University of
California Los Angeles and Geriatric Research Educational Clinical
Center, Veterans Affairs Medical Center Sepulveda, Sepulveda,
California 91343, and 3 Laboratory of Cell Regulation and
Carcinogenesis, National Institutes of Health, National Cancer
Institute, Bethesda, Maryland 20892
The transforming growth factor- (TGF-) family consists of
three isoforms and is part of a larger family of cytokines regulating differentiation, development, and tissue repair. Previous work from our
laboratory has shown that TGF-1 can increase amyloid- protein
(A) immunoreactive (Air) plaque-like deposits in rat brain. The
aim of the current study was to evaluate all three isoforms of TGF-
for their ability to affect the deposition and neurotoxicity of A in
an organotypic, hippocampal slice culture model of A deposition.
Slice cultures were treated with A either with or without one of the
TGF- isoforms. All three isoforms can increase A accumulation
(over A treatment alone) within the slice culture, as determined by
ELISA. However, there are striking differences in the pattern of Air
among the three isoforms of TGF-. Isoforms 1 and 3 produced a
cellular pattern of A staining that colocalizes with GS lectin
staining (microglia). TGF-2 produces dramatic A staining of
pyramidal neurons in layers CA1-CA2. In addition to cellular A
staining, plaque-like deposits are increased by all of the TGF-s.
Although no gross toxicity was observed, morphological
neurodegenerative changes were seen in the CA1 region when the slices
were treated with A plus TGF-2. Our results demonstrate important
functional differences among the TGF- isoforms in their ability to
alter the cellular distribution and degradation of A. These changes
may be relevant to the pathology of Alzheimer's disease (AD).
Key words:
Alzheimer's disease; aging; trauma; injury; growth
factor; amyloid
Copyright © 1998 Society for Neuroscience 0270-6474/98/182410366-09$05.00/0
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