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The Journal of Neuroscience, September 15, 2000, 20(18):7116-7121
Involvement of Brain-Derived Neurotrophic Factor in
Spatial Memory Formation and Maintenance in a Radial Arm Maze Test
in Rats
Makoto
Mizuno1,
Kiyofumi
Yamada1,
Ana
Olariu1,
Hiroyuki
Nawa2, and
Toshitaka
Nabeshima1
1 Department of Neuropsychopharmacology and Hospital
Pharmacy, Nagoya University Graduate School of Medicine, Showa-ku
Nagoya 466-8560, Japan, and 2 Department of Molecular
Neurobiology, Brain Research Institute, Niigata University, Niigata
951-8585, Japan
Brain-derived neurotrophic factor (BDNF) regulates both short-term
synaptic functions and activity-dependent synaptic plasticity such as
long-term potentiation. In the present study, we investigated the role
of BDNF in the spatial reference and working memory in a radial arm
maze test. The radial arm maze training resulted in a significant
increase in the BDNF mRNA expression in the hippocampus, although the
expression in the frontal cortex did not change. When spatial learning
was inhibited by treatment with 7-nitroindazole, an inhibitor of brain
nitric oxide synthase, the increase in the hippocampal BDNF mRNA did
not occur. To clarify the causal relation between BDNF mRNA expression
and spatial memory formation, we examined the effects of antisense BDNF
treatment on spatial learning and memory. A continuous
intracerebroventricular infusion of antisense BDNF oligonucleotide
resulted in an impairment of spatial learning, although the sense
oligonucleotide had no effect. Treatment with antisense, but not sense,
BDNF oligonucleotide was associated with a significant reduction of
BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment
with antisense BDNF oligonucleotide in rats, which had previously
acquired spatial memory by an extensive training, impaired both
reference and working memory. There were no differences in locomotor
activity, food consumption, and body weight between the antisense and
sense oligonucleotide-treated rats. These results suggest that BDNF
plays an important role not only in the formation, but also in the
retention and/or recall, of spatial memory.
Key words:
BDNF; working memory; reference memory; radial arm maze; antisense oligonucleotide; LTP; hippocampus
Copyright © 2000 Society for Neuroscience 0270-6474/00/20187116-06$05.00/0
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