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Volume 17, Number 24,
Issue of December 15, 1997
pp. 9492-9505
Activity-Dependent Dendritic Targeting of BDNF and TrkB mRNAs in
Hippocampal Neurons
Received July 23, 1997; revised Sept. 29, 1997; accepted Oct. 3, 1997.
Enrico Tongiorgi,
Massimo Righi, and
Antonino Cattaneo
International School for Advanced Studies (SISSA), Neuroscience
Program, 34014 Trieste, Italy
The mechanisms underlying the subcellular localization of
neurotrophins and their receptors are poorly understood. We show that
in cultured hippocampal neurons, the mRNAs for BDNF and TrkB have a
somatodendritic localization, and we quantify the extent of their
dendritic mRNA localization. In the dendrites the labeling covers on
average the proximal 30% of the total dendritic length. On high
potassium depolarization, the labeling of BDNF and TrkB mRNA extends on
average to 68% of the dendritic length. This increase does not depend
on new RNA synthesis, is inhibited by the Na+
channel blocker tetrodotoxin, and involves the activation of glutamate
receptors. Extracellular Ca2+, partly flowing
through L-type Ca2+ channels, is absolutely required
for this process to occur. At the protein level, a brief stimulation of
hippocampal neurons with 10 mM KCl leads to a marked
increase of BDNF and TrkB immunofluorescence density in the distal
portion of dendrites, which also occurs, even if at lower levels, when
transport is inhibited by nocodazole. The protein synthesis inhibitor
cycloheximide abolishes this increase. The activity-dependent
modulation of mRNA targeting and protein accumulation in the dendrites
may provide a mechanism for achieving a selective local regulation of
the activity of neurotrophins and their receptors, close to their sites
of action.
Key words:
neurotrophins;
dendritic mRNA;
BDNF;
TrkB;
synaptic
plasticity;
hippocampal neurons
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