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Volume 17, Number 7,
Issue of April 1, 1997
pp. 2295-2313
Copyright ©1997 Society for Neuroscience
Distribution of Brain-Derived Neurotrophic Factor (BDNF) Protein
and mRNA in the Normal Adult Rat CNS: Evidence for Anterograde Axonal
Transport
Received Aug. 9, 1996; revised Dec. 12, 1996; accepted Jan. 17, 1997.
James M. Conner1,
Julie
C. Lauterborn2,
Qiao Yan3,
Christine M. Gall2, and
Silvio Varon1
1 Department of Biology, 0506, University of
California, San Diego, La Jolla, California 92093, 2 Department of Anatomy and Neurobiology, University of
California, Irvine, California 92697, and 3 Amgen Center,
Thousand Oaks, California 91320
A sensitive immunohistochemical technique was used, along with
highly specific affinity-purified antibodies to brain-derived neurotrophic factor (BDNF), to generate a detailed mapping of BDNF
immunoreactivity (BDNF-ir) throughout the adult rat CNS. A parallel
analysis of sites of BDNF synthesis was performed with in
situ hybridization techniques using a cRNA probe to the exon encoding mature rat BDNF protein. These combined data revealed (1)
groups of cell bodies containing diffuse BDNF-ir throughout the CNS
that were strongly correlated with fields of cells containing BDNF
mRNA; (2) varying degrees of BDNF-ir outside of cell bodies, in what
appeared to be fibers and/or terminals; and (3) many regions containing
extremely heavy BDNF-immunoreactive fiber/terminal labeling that lacked
BDNF mRNA (e.g., medial habenula, central nucleus of the amygdala, bed
nucleus of stria terminalis, lateral septum, and spinal cord). The
latter observation suggested that in these regions BDNF was derived
from anterograde axonal transport by afferent systems. In the two cases
in which this hypothesis was tested by the elimination of select
afferents, BDNF immunostaining was completely eliminated. These data,
along with the observation that BDNF-ir was rarely found within
dendrites or fibers en passage, suggest that BDNF
protein produced in adult CNS neurons is polarized primarily along
axonal processes and is preferentially stored in terminals within the
innervation target.
Key words:
neurotrophin;
immunohistochemistry;
in situ
hybridization;
neurotrophic factor;
BDNF;
anterograde axonal
transport
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J. R. Tonra, R. Curtis, V. Wong, K. D. Cliffer, J. S. Park, A. Timmes, T. Nguyen, R. M. Lindsay, A. Acheson, and P. S. DiStefano
Axotomy Upregulates the Anterograde Transport and Expression of Brain-Derived Neurotrophic Factor by Sensory Neurons
J. Neurosci.,
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[Abstract]
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J. P. Fawcett, S. X. Bamji, C. G. Causing, R. Aloyz, A. R. Ase, T. A. Reader, J. H. McLean, and F. D. Miller
Functional Evidence that BDNF Is an Anterograde Neuronal Trophic Factor in the CNS
J. Neurosci.,
April 15, 1998;
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[Abstract]
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W Haubensak, F Narz, R Heumann, and V Lessmann
BDNF-GFP containing secretory granules are localized in the vicinity of synaptic junctions of cultured cortical neurons
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[Abstract]
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E. Messaoudi, K. Bardsen, B. Srebro, and C. R. Bramham
Acute Intrahippocampal Infusion of BDNF Induces Lasting Potentiation of Synaptic Transmission in the Rat Dentate Gyrus
J Neurophysiol,
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E. Tongiorgi, M. Righi, and A. Cattaneo
Activity-Dependent Dendritic Targeting of BDNF and TrkB mRNAs in Hippocampal Neurons
J. Neurosci.,
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G. J. Michael, S. Averill, A. Nitkunan, M. Rattray, D. L. H. Bennett, Q. Yan, and J. V. Priestley
Nerve Growth Factor Treatment Increases Brain-Derived Neurotrophic Factor Selectively in TrkA-Expressing Dorsal Root Ganglion Cells and in Their Central Terminations within the Spinal Cord
J. Neurosci.,
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[Abstract]
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H. E. Scharfman
Hyperexcitability in Combined Entorhinal/Hippocampal Slices of Adult Rat After Exposure to Brain-Derived Neurotrophic Factor
J Neurophysiol,
August 1, 1997;
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1082 - 1095.
[Abstract]
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C. Zuccato, A. Ciammola, D. Rigamonti, B. R. Leavitt, D. Goffredo, L. Conti, M. E. MacDonald, R. M. Friedlander, V. Silani, M. R. Hayden, et al.
Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease
Science,
July 20, 2001;
293(5529):
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[Abstract]
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C.-W. Xie, D. Sayah, Q.-S. Chen, W.-Z. Wei, D. Smith, and X. Liu
Deficient long-term memory and long-lasting long-term potentiation in mice with a targeted deletion of neurotrophin-4 gene
PNAS,
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[Abstract]
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