 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 13, 3394-3405, Copyright © 1993 by Society for Neuroscience
Cultured hippocampal neurons show responses to BDNF, NT-3, and NT-4, but not NGF
NY Ip, Y Li, GD Yancopoulos and RM Lindsay
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
To investigate the possibility of neurotrophins acting directly on
hippocampal neurons, we first examined expression of the trk receptors in
sections of adult rat brain and in cultures of embryonic rat hippocampus,
and then investigated general and specific responses of cultured
hippocampal neurons to each of the neurotrophins. In situ hybridization
studies indicated high levels of expression of trkB and trkC but not trkA
in pyramidal cells, dentate granule neurons, and scattered interneurons.
Cultures of embryonic day 18 (E18) hippocampal neurons were also found by
Northern analysis to express trkB and trkC but not trkA, indicating
potential responsiveness to brain-derived neurotrophic factor (BDNF),
neurotrophin-3 (NT-3), and NT-4, but not NGF. Phosphorylation experiments
indeed showed that BDNF, NT-3, and NT- 4 produced rapid tyrosine
phosphorylation of Trk proteins, as detected by immunoprecipitation using a
pan-Trk-specific antibody, whereas NGF produced no detectable tyrosine
phosphorylation in hippocampal cultures. Similarly, all of the
neurotrophins, except NGF, induced expression of c-fos mRNA and c-fos
protein in these cultures. c-Fos protein induction was detectable in
approximately 40-50% of the cells. While we observed no major effect of any
of the neurotrophins upon the survival of E18 hippocampal neurons, BDNF,
NT-3, and NT-4, but not NGF, produced marked increases in the number of
neurons expressing detectable levels of either calbindin or AChE. NT-3
produced the greatest increase in the number of calbindin-positive neurons,
whereas BDNF and NT-4 produced the greater increase in the number of AChE-
positive neurons. Our results suggest that several of the neurotrophins
have important effects in the differentiation and maintenance of function
of subpopulations of hippocampal neurons.
This article has been cited by other articles:
|
|
|
|
 
J. Zheng, W.-H. Shen, T.-J. Lu, Y. Zhou, Q. Chen, Z. Wang, T. Xiang, Y.-C. Zhu, C. Zhang, S. Duan, et al.
Clathrin-dependent Endocytosis Is Required for TrkB-dependent Akt-mediated Neuronal Protection and Dendritic Growth
J. Biol. Chem.,
May 9, 2008;
283(19):
13280 - 13288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. E. Cosker, S. Shadan, M. van Diepen, C. Morgan, M. Li, V. Allen-Baume, C. Hobbs, P. Doherty, S. Cockcroft, and B. J. Eickholt
Regulation of PI3K signalling by the phosphatidylinositol transfer protein PITP{alpha} during axonal extension in hippocampal neurons
J. Cell Sci.,
March 15, 2008;
121(6):
796 - 803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hisata, T. Sakisaka, T. Baba, T. Yamada, K. Aoki, M. Matsuda, and Y. Takai
Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth
J. Cell Biol.,
August 27, 2007;
178(5):
843 - 860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kohara, H. Yasuda, Y. Huang, N. Adachi, K. Sohya, and T. Tsumoto
A Local Reduction in Cortical GABAergic Synapses after a Loss of Endogenous Brain-Derived Neurotrophic Factor, as Revealed by Single-Cell Gene Knock-Out Method
J. Neurosci.,
July 4, 2007;
27(27):
7234 - 7244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Shinoda, S. Taya, D. Tsuboi, T. Hikita, R. Matsuzawa, S. Kuroda, A. Iwamatsu, and K. Kaibuchi
DISC1 Regulates Neurotrophin-Induced Axon Elongation via Interaction with Grb2
J. Neurosci.,
January 3, 2007;
27(1):
4 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Massa, Y. Xie, T. Yang, A. W. Harrington, M. L. Kim, S. O. Yoon, R. Kraemer, L. A. Moore, B. L. Hempstead, and F. M. Longo
Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death.
J. Neurosci.,
May 17, 2006;
26(20):
5288 - 5300.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. X. Soriano, S. Papadia, F. Hofmann, N. R. Hardingham, H. Bading, and G. E. Hardingham
Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability.
J. Neurosci.,
April 26, 2006;
26(17):
4509 - 4518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hartmann, T. Brigadski, K. S. Erdmann, B. Holtmann, M. Sendtner, F. Narz, and V. Lessmann
Truncated TrkB receptor-induced outgrowth of dendritic filopodia involves the p75 neurotrophin receptor
J. Cell Sci.,
November 15, 2004;
117(24):
5803 - 5814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Koyama, M. K. Yamada, S. Fujisawa, R. Katoh-Semba, N. Matsuki, and Y. Ikegaya
Brain-Derived Neurotrophic Factor Induces Hyperexcitable Reentrant Circuits in the Dentate Gyrus
J. Neurosci.,
August 18, 2004;
24(33):
7215 - 7224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kohara, A. Kitamura, N. Adachi, M. Nishida, C. Itami, S. Nakamura, and T. Tsumoto
Inhibitory But Not Excitatory Cortical Neurons Require Presynaptic Brain-Derived Neurotrophic Factor for Dendritic Development, as Revealed by Chimera Cell Culture
J. Neurosci.,
July 9, 2003;
23(14):
6123 - 6131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Cheng, S. Wang, D. Yang, R. Xiao, and M. P. Mattson
Calmodulin Mediates Brain-derived Neurotrophic Factor Cell Survival Signaling Upstream of Akt Kinase in Embryonic Neocortical Neurons
J. Biol. Chem.,
February 21, 2003;
278(9):
7591 - 7599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Mattson, S. L. Chan, and W. Duan
Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior
Physiol Rev,
July 1, 2002;
82(3):
637 - 672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Dorsey, L. L. Bambrick, R. J. Balice-Gordon, and B. K. Krueger
Failure of Brain-Derived Neurotrophic Factor-Dependent Neuron Survival in Mouse Trisomy 16
J. Neurosci.,
April 1, 2002;
22(7):
2571 - 2578.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Oksvold, E. Skarpen, J. Widerberg, and H. S. Huitfeldt
Fluorescent Histochemical Techniques for Analysis of Intracellular Signaling
J. Histochem. Cytochem.,
March 1, 2002;
50(3):
289 - 303.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Boukhaddaoui, V. Sieso, F. Scamps, and J. Valmier
An Activity-Dependent Neurotrophin-3 Autocrine Loop Regulates the Phenotype of Developing Hippocampal Pyramidal Neurons before Target Contact
J. Neurosci.,
November 15, 2001;
21(22):
8789 - 8797.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Roosen, A. Schober, J. Strelau, M. Bottner, J. Faulhaber, G. Bendner, S. L. McIlwrath, H. Seller, H. Ehmke, G. R. Lewin, et al.
Lack of Neurotrophin-4 Causes Selective Structural and Chemical Deficits in Sympathetic Ganglia and Their Preganglionic Innervation
J. Neurosci.,
May 1, 2001;
21(9):
3073 - 3084.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Beattie, C. L. Howe, A. Wilde, F. M. Brodsky, and W. C. Mobley
NGF Signals through TrkA to Increase Clathrin at the Plasma Membrane and Enhance Clathrin-Mediated Membrane Trafficking
J. Neurosci.,
October 1, 2000;
20(19):
7325 - 7333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Xu, W. Gottschalk, A. Chow, R. I. Wilson, E. Schnell, K. Zang, D. Wang, R. A. Nicoll, B. Lu, and L. F. Reichardt
The Role of Brain-Derived Neurotrophic Factor Receptors in the Mature Hippocampus: Modulation of Long-Term Potentiation through a Presynaptic Mechanism involving TrkB
J. Neurosci.,
September 15, 2000;
20(18):
6888 - 6897.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Friedman
Neurotrophins Induce Death of Hippocampal Neurons via the p75 Receptor
J. Neurosci.,
September 1, 2000;
20(17):
6340 - 6346.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-R. Schabitz, C. Sommer, W. Zoder, M. Kiessling, M. Schwaninger, S. Schwab, and S. P. Finklestein
Intravenous Brain-Derived Neurotrophic Factor Reduces Infarct Size and Counterregulates Bax and Bcl-2 Expression After Temporary Focal Cerebral Ischemia Editorial Comment
Stroke,
September 1, 2000;
31(9):
2212 - 2217.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Bolton, A. J. Pittman, and D. C. Lo
Brain-Derived Neurotrophic Factor Differentially Regulates Excitatory and Inhibitory Synaptic Transmission in Hippocampal Cultures
J. Neurosci.,
May 1, 2000;
20(9):
3221 - 3232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Fawcett, M. A. Alonso-Vanegas, S. J. Morris, F. D. Miller, A. F. Sadikot, and R. A. Murphy
Evidence that Brain-Derived Neurotrophic Factor from Presynaptic Nerve Terminals Regulates the Phenotype of Calbindin-Containing Neurons in the Lateral Septum
J. Neurosci.,
January 1, 2000;
20(1):
274 - 282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. T. Sherwood and D. C. Lo
Long-Term Enhancement of Central Synaptic Transmission by Chronic Brain-Derived Neurotrophic Factor Treatment
J. Neurosci.,
August 15, 1999;
19(16):
7025 - 7036.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ikeda, H. Tanihara, Y. Honda, T. Tatsuno, H. Noguchi, and C. Nakayama
BDNF Attenuates Retinal Cell Death Caused by Chemically Induced Hypoxia in Rats
Invest. Ophthalmol. Vis. Sci.,
August 1, 1999;
40(9):
2130 - 2140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-B. Gao and A N van den Pol
Neurotrophin-3 potentiates excitatory GABAergic synaptic transmission in cultured developing hypothalamic neurones of the rat
J. Physiol.,
July 1, 1999;
518(1):
81 - 95.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. B. Knowles and K. S. Kosik
Neurotrophin-3 signals redistribute RNA in neurons
PNAS,
December 23, 1997;
94(26):
14804 - 14808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yajima, C.-H. Lammers, S.-H. Lee, Y. Hara, K. Mizuno, and M. M. Mouradian
Cloning and Characterization of Murine Glial Cell-Derived Neurotrophic Factor Inducible Transcription Factor (MGIF)
J. Neurosci.,
November 15, 1997;
17(22):
8657 - 8666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Jarvis, Z.-G. Xiong, J. R. Plant, D. Churchill, W.-Y. Lu, B. A. Macvicar, and J. F. Macdonald
Neurotrophin Modulation of NMDA Receptors in Cultured Murine and Isolated Rat Neurons
J Neurophysiol,
November 1, 1997;
78(5):
2363 - 2371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Akaneya, T. Tsumoto, S. Kinoshita, and H. Hatanaka
Brain-Derived Neurotrophic Factor Enhances Long-Term Potentiation in Rat Visual Cortex
J. Neurosci.,
September 1, 1997;
17(17):
6707 - 6716.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Kossel, C. V. Williams, M. Schweizer, and S. B. Kater
Afferent Innervation Influences the Development of Dendritic Branches and Spines via Both Activity-Dependent and Non-Activity-Dependent Mechanisms
J. Neurosci.,
August 15, 1997;
17(16):
6314 - 6324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Scharfman
Hyperexcitability in Combined Entorhinal/Hippocampal Slices of Adult Rat After Exposure to Brain-Derived Neurotrophic Factor
J Neurophysiol,
August 1, 1997;
78(2):
1082 - 1095.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Adams, M. Sazgar, P. Osehobo, C. E. E. M. Van der Zee, J. Diamond, M. Fahnestock, and R. J. Racine
Nerve Growth Factor Accelerates Seizure Development, Enhances Mossy Fiber Sprouting, and Attenuates Seizure-Induced Decreases in Neuronal Density in the Kindling Model of Epilepsy
J. Neurosci.,
July 15, 1997;
17(14):
5288 - 5296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Alcantara, J. Frisen, J. A. del Rio, E. Soriano, M. Barbacid, and I. Silos-Santiago
TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death
J. Neurosci.,
May 15, 1997;
17(10):
3623 - 3633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. A. Vaidya, G. J. Marek, G. K. Aghajanian, and R. S. Duman
5-HT2A Receptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex
J. Neurosci.,
April 15, 1997;
17(8):
2785 - 2795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Daly and E. B. Ziff
Post-Transcriptional Regulation of Synaptic Vesicle Protein Expression and the Developmental Control of Synaptic Vesicle Formation
J. Neurosci.,
April 1, 1997;
17(7):
2365 - 2375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Lauterborn, S. Rivera, C. T. Stinis, V. Y. Hayes, P. J. Isackson, and C. M. Gall
Differential Effects of Protein Synthesis Inhibition on the Activity-Dependent Expression of BDNF Transcripts: Evidence for Immediate-Early Gene Responses from Specific Promoters
J. Neurosci.,
December 1, 1996;
16(23):
7428 - 7436.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L Minichiello and R Klein
TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons.
Genes & Dev.,
November 15, 1996;
10(22):
2849 - 2858.
[Abstract]
[PDF]
|
|
|
|
|
|
|
H. Kang and E. M. Schuman
A Requirement for Local Protein Synthesis in Neurotrophin-Induced Hippocampal Synaptic Plasticity
Science,
September 6, 1996;
273(5280):
1402 - 1406.
[Abstract]
|
|
|
|
|
|
|
Y. Watanabe, R. S. Johnson, L. S. Butler, D. K. Binder, B. M. Spiegelman, V. E. Papaioannou, and J. O. McNamara
Null Mutation of c-fos Impairs Structural and Functional Plasticities in the Kindling Model of Epilepsy
J. Neurosci.,
June 15, 1996;
16(12):
3827 - 3836.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H Kang, L Z Jia, K Y Suh, L Tang, and E M Schuman
Determinants of BDNF-induced hippocampal synaptic plasticity: role of the Trk B receptor and the kinetics of neurotrophin delivery.
Learn. Mem.,
January 1, 1996;
3(2-3):
188 - 196.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Finkbeiner
Calcium-mediated Gene Expression: Mechanism for Neuronal Plasticity and Survival
Neuroscientist,
November 1, 1995;
1(6):
317 - 320.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. S. Duman, V. A. Vaidya, M. Nibuya, S. Morinobu, and L. R. Fitzgerald
Review : Stress, Antidepressant Treatments, and Neurotrophic Factors: Molecular and Cellular Mechanisms
Neuroscientist,
November 1, 1995;
1(6):
351 - 360.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B Berninger, S Marty, F Zafra, M da Penha Berzaghi, H Thoenen, and D Lindholm
GABAergic stimulation switches from enhancing to repressing BDNF expression in rat hippocampal neurons during maturation in vitro
Development,
January 8, 1995;
121(8):
2327 - 2335.
[Abstract]
[PDF]
|
|
|
|
|
|
|
L. P. Henderson, L. Lin, A. Prasad, C. A. Paul, T. Y. Chang, and R. A. Maue
Embryonic Striatal Neurons from Niemann-Pick Type C Mice Exhibit Defects in Cholesterol Metabolism and Neurotrophin Responsiveness
J. Biol. Chem.,
June 23, 2000;
275(26):
20179 - 20187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
