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Blocking Nerve Growth Factor Binding To The P75 Neurotrophin Receptor On Sympathetic Neurons Transiently Reduces Trka Activation But Does Not Affect Neuronal Survival, C. Lachance, Daniel Belliveau, P. Barker Dec 1996

Blocking Nerve Growth Factor Binding To The P75 Neurotrophin Receptor On Sympathetic Neurons Transiently Reduces Trka Activation But Does Not Affect Neuronal Survival, C. Lachance, Daniel Belliveau, P. Barker

Daniel J. Belliveau

Nerve growth factor interacts with the trkA tyrosine kinase receptor and with the p75 neurotrophin receptor. It is clear that trkA mediates most, if not all, of the stereotypical responses of sympathetic neurons to nerve growth factor but the role of the p75 neurotrophin receptor is unclear. In this study, we have asked whether a functional interaction between p75 neurotrophin receptor and trkA exists in primary sympathetic neurons by disrupting nerve growth factor binding to p75 neurotrophin receptor. Acute assays reveal that blocking antibodies directed against p75 neurotrophin receptor reduce nerve growth factor-mediated trkA tyrosine phosphorylation and reduce the amount …


Transgenic Mice Expressing The Intracellular Domain Of The P75 Neurotrophin Receptor Undergo Neuronal Apoptosis, M. Majdan, C. Lachance, A. Gloster, R. Aloyz, C. Zeindler, S. Bamji, A. Bhakar, Daniel Belliveau, J. Fawcett, F. Miller, P. Barker Dec 1996

Transgenic Mice Expressing The Intracellular Domain Of The P75 Neurotrophin Receptor Undergo Neuronal Apoptosis, M. Majdan, C. Lachance, A. Gloster, R. Aloyz, C. Zeindler, S. Bamji, A. Bhakar, Daniel Belliveau, J. Fawcett, F. Miller, P. Barker

Daniel J. Belliveau

We have asked whether p75NTR may play a role in neuronal apoptosis by producing transgenic mice that express the p75NTR intracellular domain within peripheral and central neurons. These animals showed profound reductions in numbers of sympathetic and peripheral sensory neurons as well as cell loss in the neocortex, where there is normally little or no p75NTR expression. Developmental loss of facial motor neurons was not observed, but induced expression of the p75NTR intracellular domain within adult animals led to increased motor neuron death after axotomy. Biochemical analyses suggest that these effects were not attributable to a p75NTR-dependent reduction in trk …


Ngf And Neurotrophin-3 Both Activate Trka On Sympathetic Neurons But Differentially Regulate Survival And Neuritogenesis, Daniel Belliveau, I. Krivko, C. Lachance, J. Kohn, D. Rusakov, D. Kaplan, F. Miller Dec 1996

Ngf And Neurotrophin-3 Both Activate Trka On Sympathetic Neurons But Differentially Regulate Survival And Neuritogenesis, Daniel Belliveau, I. Krivko, C. Lachance, J. Kohn, D. Rusakov, D. Kaplan, F. Miller

Daniel J. Belliveau

In this report we examine the biological and molecular basis of the control of sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3). NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth-associated genes in NGF-dependent sympathetic neurons, but it is 20-40-fold less efficient in supporting their survival. Both NT-3 and NGF induce similar sustained, long-term activation of TrkA, while NGF is 10-fold more efficient than NT-3 in mediating acute, short-term TrkA activity. At similar acute levels of TrkA activation, NT-3 still mediates neuronal survival two- to threefold less well than NGF. However, a mutant NT-3 …


Adenovirus-Mediated Gene Transfer Of The Tumor Suppressor, P53, Induces Apoptosis In Postmitotic Neurons, R. Slack, Daniel Belliveau, M. Rosenberg, J. Atwal, H. Lochmuller, R. Aloyz, A. Haghighi, B. Lach, P. Seth, E. Cooper, F. Miller Dec 1995

Adenovirus-Mediated Gene Transfer Of The Tumor Suppressor, P53, Induces Apoptosis In Postmitotic Neurons, R. Slack, Daniel Belliveau, M. Rosenberg, J. Atwal, H. Lochmuller, R. Aloyz, A. Haghighi, B. Lach, P. Seth, E. Cooper, F. Miller

Daniel J. Belliveau

Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found …


Cortical Type 2 Astrocytes Are Not Dye Coupled Nor Do They Express The Major Gap Junction Genes Found In The Central Nervous System, Daniel Belliveau, C. Naus Dec 1993

Cortical Type 2 Astrocytes Are Not Dye Coupled Nor Do They Express The Major Gap Junction Genes Found In The Central Nervous System, Daniel Belliveau, C. Naus

Daniel J. Belliveau

The O‐2A progenitor cell first described from the rat optic nerve is a bipotential precursor of oligodendrocytes and type 2 astrocytes. Each cell expresses specific markers that distinguish them as unique cell types. O‐2A progenitors cultured in high serum preferentially differntiate into type 2 astrocytes and when exposed to defined medium or low serum develop along the oligodendrocyte lineage. We analyzed the gap junction gene expression of type 2 astrocytes to determine if they are coupled to form a syncytium, like their type 1 astrocyte counterparts. Dye coupling experiments demonstrated that cortical type 2 astrocytes are not coupled, while type …


In Vivo Growth Of C6 Glioma Cells Transfected With Connexin43 Cdna, C. Naus, K. Elisevich, D. Zhu, Daniel Belliveau, R. Del Maestro Dec 1991

In Vivo Growth Of C6 Glioma Cells Transfected With Connexin43 Cdna, C. Naus, K. Elisevich, D. Zhu, Daniel Belliveau, R. Del Maestro

Daniel J. Belliveau

In order to examine the possible role of intercellular communication via gap junctions in the control of tumor growth, we have transfected C6 glioma cells with connexin43 cDNA. We obtained several clones with variable expression of connexin43. The growth rate of these clones in culture was inversely related to the degree of expression of the transfected cDNA. To examine the growth of these transfected cells in vivo, cells were grown in spinner culture flasks to form spheroids 250–300 µm in diameter. Spheroids of nontransfected C6 cells produced large gliomas. Immunohistochemical and in situ hybridization analyses revealed relatively high levels of …


Regional Differences In Connexin32 And Connexin43 Messenger Rnas In Rat Brain, C. Naus, Daniel Belliveau, J. Bechberger Dec 1989

Regional Differences In Connexin32 And Connexin43 Messenger Rnas In Rat Brain, C. Naus, Daniel Belliveau, J. Bechberger

Daniel J. Belliveau

The regional distribution of gap junction mRNAs was examined in the adult rat brain. The level of connexin43 mRNA is more abundant than connexin32, being homogeneously distributed throughout different regions of brain. In contrast, there is dramatic heterogeneity in the level of connexin32 mRNA, with the highest level in the hindbrain. These results suggest that the gap junction genes are differentially expressed in regions of the adult rat brain.