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(Received for publication, November 15, 1996, and in revised form, January 30, 1997)
and
From the Centre for Neuronal Survival, The mRNA encoding brain-derived neurotrophic
factor (BDNF) is widely distributed in central nervous system neurons,
including in hippocampus and cortex. However, little is known about the physiology of BDNF protein within neurons, including how it is processed or packaged and the mechanisms that control its release. In
this study, we have used antibodies to monitor the subcellular distribution of BDNF in cortical extracts from adult rats treated with
kainic acid. BDNF immunoreactivity is elevated in rat cortex 12 h
after kainic acid treatment. The protein is enriched in a vesicular
fraction isolated from lysed synaptosomes, its distribution being
similar to that of synaptotagmin, which is associated with synaptic
vesicles and large dense core vesicles at nerve terminals. The
vesicular pool of BDNF is digested by proteinase K only in the presence
of Triton X-100 suggesting localization of BDNF in membrane fractions.
Immunocytochemistry detects diffuse and punctate BDNF staining within
cell bodies and processes of cortical neurons from kainic
acid-treated rats, as well as in mossy fiber terminals of rat
hippocampus. Taken together, these data show that BDNF can accumulate
axonally within a vesicular compartment of brain neurons. Results
support the idea that endogenous BDNF may be transported anterogradely
and released by regulated secretory mechanisms.
Cell Biology of
Excitable Tissue Group, Montreal Neurological Institute, McGill
University, Montreal, Quebec H3A 2B4, Canada and the
§ Division of Basic Medical Sciences, Memorial University of
Newfoundland, St. John's, Newfoundland A1B 3V6, Canada
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