scholarly journals TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal

2001 ◽  
Vol 155 (7) ◽  
pp. 1275-1286 ◽  
Author(s):  
Marta Majdan ◽  
Gregory S. Walsh ◽  
Raquel Aloyz ◽  
Freda D. Miller
Keyword(s):  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Neurotrophin Receptor ◽  
Primary Neurons ◽  
P75 Neurotrophin Receptor ◽  
Neuron Death ◽  
Ngf Receptor ◽  
Survival Signaling ◽  
Apoptotic Signal

Developmental sympathetic neuron death is determined by functional interactions between the TrkA/NGF receptor and the p75 neurotrophin receptor (p75NTR). A key question is whether p75NTR promotes apoptosis by directly inhibiting or modulating TrkA activity, or by stimulating cell death independently of TrkA. Here we provide evidence for the latter model. Specifically, experiments presented here demonstrate that the presence or absence of p75NTR does not alter Trk activity or NGF- and NT-3–mediated downstream survival signaling in primary neurons. Crosses of p75NTR−/− and TrkA−/− mice indicate that the coincident absence of p75NTR substantially rescues TrkA−/− sympathetic neurons from developmental death in vivo. Thus, p75NTR induces death regardless of the presence or absence of TrkA expression. These data therefore support a model where developing sympathetic neurons are “destined to die” by an ongoing p75NTR-mediated apoptotic signal, and one of the major ways that TrkA promotes neuronal survival is by silencing this ongoing death signal.

scholarly journals The p75 Neurotrophin Receptor Mediates Neuronal Apoptosis and Is Essential for Naturally Occurring Sympathetic Neuron Death

1998 ◽  
Vol 140 (4) ◽  
pp. 911-923 ◽  
Author(s):  
Shernaz X. Bamji ◽  
Marta Majdan ◽  
Christine D. Pozniak ◽  
Daniel J. Belliveau ◽  
Raquel Aloyz ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Neurotrophin Receptor ◽  
Tyrosine Kinase Receptor ◽  
P75 Neurotrophin Receptor ◽  
Neuron Death ◽  
Naturally Occurring ◽  
Physiological Relevance ◽  
Normal Period

Abstract. To determine whether the p75 neurotrophin receptor (p75NTR) plays a role in naturally occurring neuronal death, we examined neonatal sympathetic neurons that express both the TrkA tyrosine kinase receptor and p75NTR. When sympathetic neuron survival is maintained with low quantities of NGF or KCl, the neurotrophin brain-derived neurotrophic factor (BDNF), which does not activate Trk receptors on sympathetic neurons, causes neuronal apoptosis and increased phosphorylation of c-jun. Function-blocking antibody studies indicate that this apoptosis is due to BDNF-mediated activation of p75NTR. To determine the physiological relevance of these culture findings, we examined sympathetic neurons in BDNF−/− and p75NTR−/− mice. In BDNF−/− mice, sympathetic neuron number is increased relative to BDNF+/+ littermates, and in p75NTR−/− mice, the normal period of sympathetic neuron death does not occur, with neuronal attrition occurring later in life. This deficit in apoptosis is intrinsic to sympathetic neurons, since cultured p75NTR−/− neurons die more slowly than do their wild-type counterparts. Together, these data indicate that p75NTR can signal to mediate apoptosis, and that this mechanism is essential for naturally occurring sympathetic neuron death.

The p75 neurotrophin receptor influences NT-3 responsiveness of sympathetic neurons in vivo

10.1038/11158 ◽  
1999 ◽  
Vol 2 (8) ◽  
pp. 699-705 ◽  
Author(s):  
Christine Brennan ◽  
Kimberly Rivas-Plata ◽  
Story C. Landis
Keyword(s):  
Sympathetic Neurons ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

scholarly journals Retrograde apoptotic signaling by the p75 neurotrophin receptor

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Amrita Pathak ◽  
Bruce D. Carter
Keyword(s):  
System Development ◽  
Nervous System Development ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Cell Soma ◽  
Apoptotic Signaling ◽  
Survival Signaling ◽  
P75 Receptor ◽  
Apoptotic Signal

Neurotrophins are target-derived factors necessary for mammalian nervous system development and maintenance. They are typically produced by neuronal target tissues and interact with their receptors at axonal endings. Therefore, locally generated neurotrophin signals must be conveyed from the axon back to the cell soma. Retrograde survival signaling by neurotrophin binding to Trk receptors has been extensively studied. However, neurotrophins also bind to the p75 receptor, which can induce apoptosis in a variety of contexts. Selective activation of p75 at distal axon ends has been shown to generate a retrograde apoptotic signal, although the mechanisms involved are poorly understood. The present review summarizes the available evidence for retrograde proapoptotic signaling in general and the role of the p75 receptor in particular, with discussion of unanswered questions in the field. In-depth knowledge of the mechanisms of retrograde apoptotic signaling is essential for understanding the etiology of neurodegeneration in many diseases and injuries.

scholarly journals P53 Is Essential for Developmental Neuron Death as Regulated by the TrkA and p75 Neurotrophin Receptors

1998 ◽  
Vol 143 (6) ◽  
pp. 1691-1703 ◽  
Author(s):  
Raquel S. Aloyz ◽  
Shernaz X. Bamji ◽  
Christine D. Pozniak ◽  
Jean G. Toma ◽  
Jasvinder Atwal ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
P53 Protein ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Neurotrophin Receptor ◽  
Neuron Death ◽  
Jnk Pathway ◽  
Common Component ◽  
Apoptotic Signaling ◽  
Naturally Occurring

Naturally occurring sympathetic neuron death is the result of two apoptotic signaling events: one normally suppressed by NGF/TrkA survival signals, and a second activated by the p75 neurotrophin receptor. Here we demonstrate that the p53 tumor suppressor protein, likely as induced by the MEKK-JNK pathway, is an essential component of both of these apoptotic signaling cascades. In cultured neonatal sympathetic neurons, p53 protein levels are elevated in response to both NGF withdrawal and p75NTR activation. NGF withdrawal also results in elevation of a known p53 target, the apoptotic protein Bax. Functional ablation of p53 using the adenovirus E1B55K protein inhibits neuronal apoptosis as induced by either NGF withdrawal or p75 activation. Direct stimulation of the MEKK-JNK pathway using activated MEKK1 has similar effects; p53 and Bax are increased and the subsequent neuronal apoptosis can be rescued by E1B55K. Expression of p53 in sympathetic neurons indicates that p53 functions downstream of JNK and upstream of Bax. Finally, when p53 levels are reduced or absent in p53+/− or p53−/− mice, naturally occurring sympathetic neuron death is inhibited. Thus, p53 is an essential common component of two receptor-mediated signal transduction cascades that converge on the MEKK-JNK pathway to regulate the developmental death of sympathetic neurons.

scholarly journals Ligand-Dependent Cleavage of the P75 Neurotrophin Receptor Is Necessary for NRIF Nuclear Translocation and Apoptosis in Sympathetic Neurons

Neuron ◽  
2006 ◽  
Vol 50 (2) ◽  
pp. 219-232 ◽  
Author(s):  
Rajappa S. Kenchappa ◽  
Niccolò Zampieri ◽  
Moses V. Chao ◽  
Philip A. Barker ◽  
Henry K. Teng ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Sympathetic Neurons ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

scholarly journals The p75 Neurotrophin Receptor Promotes Amyloid- (1-42)-Induced Neuritic Dystrophy In Vitro and In Vivo

2009 ◽  
Vol 29 (34) ◽  
pp. 10627-10637 ◽  
Author(s):  
J. K. Knowles ◽  
J. Rajadas ◽  
T.-V. V. Nguyen ◽  
T. Yang ◽  
M. C. LeMieux ◽  
...  
Keyword(s):  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Neuritic Dystrophy

scholarly journals p75 Neurotrophin Receptor Regulates the Timing of the Maturation of Cortical Parvalbumin Cell Connectivity and Promotes Ocular Dominance Plasticity in Adult Visual Cortex

2018 ◽  
Author(s):  
Elie Baho ◽  
Bidisha Chattopadhyaya ◽  
Marisol Lavertu-Jolin ◽  
Raffaele Mazziotti ◽  
Patricia N Awad ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Conditional Knockout ◽  
Neurotrophin Receptor ◽  
Proximity Ligation Assay ◽  
P75 Neurotrophin Receptor ◽  
Wide Range ◽  
Pv Cell

SummaryBy virtue of their extensive axonal arborisation and perisomatic synaptic targeting, cortical inhibitory Parvalbumin (PV) cells strongly regulate principal cell output and plasticity. An interesting aspect of PV cell connectivity is its prolonged maturation time course, which is completed only by end of adolescence. The p75 neurotrophin receptor (p75NTR) regulates a wide range of cellular function, including apoptosis, neuronal process remodeling and synaptic plasticity, however its role on cortical circuit development is still not well understood, mainly because localizing p75NTR expression with cellular and temporal resolution has, so far, been challenging.Using RNAscope and a modified version of the Proximity Ligation Assay (PLA), we show that p75NTR mRNA and protein are expressed in cortical PV cells in the postnatal and adult brain. Further, p75NTR expression in PV cells decreases between postnatal day (P)14 and P26, at a time when PV cell synapse numbers increase dramatically. Conditional knockout of p75NTR in single PV neurons in cortical organotypic cultures and in PV cell networks in vivo leads to precocious formation of PV cell perisomatic innervation and perineural nets around PV cell somata, suggesting that p75NTR expression controls the timing of the maturation of PV cell connectivity in the adolescent cortex.Remarkably, we found that p75NTR is still expressed, albeit at low level, in PV cells in adult cortex. Interestingly, activation of p75NTR onto PV cells in adult visual cortex in vivo is sufficient to destabilize their connectivity and to reintroduce juvenile-like cortical plasticity following monocular deprivation. Altogether, our results show that p75NTR activation dynamically regulates PV cell connectivity, and represents a novel tool to foster brain plasticity in adults.

scholarly journals Sympathetic neuroblasts undergo a developmental switch in trophic dependence

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 597-610 ◽  
Author(s):  
S.J. Birren ◽  
L. Lo ◽  
D.J. Anderson
Keyword(s):  
Neurotrophic Factors ◽  
Sympathetic Neurons ◽  
Neurotrophin Receptor ◽  
Neurotrophin 3 ◽  
Bona Fide ◽  
Neuronal Number ◽  
High Doses ◽  
Developmental Switch

Sympathetic neurons require NGF for survival, but it is not known when these cells first become dependent on neurotrophic factors. We have examined in vitro mitotically active sympathetic neuroblasts immuno-isolated from different embryonic stages, and have correlated this functional data with the expression of neurotrophin receptor mRNAs in vivo. Cells from E14.5 ganglia are supported by neurotrophin-3 (NT-3) in a serum-free medium, but not by NGF; NT-3 acts as a bona fide survival factor for these cells and not simply as a mitogen. By birth, sympathetic neurons are well-supported by NGF, whereas NT-3 supports survival only weakly and at very high doses. This change in neurotrophin-responsiveness is correlated with a reciprocal switch in the expression of trkC and trkA mRNAs by sympathetic neuroblasts in vivo. These data suggest that neurotrophic factors may control neuronal number at earlier stages of development than previously anticipated. They also suggest that the acquisition of NGF-dependence may occur, at least in part, through the loss of receptors for these interim survival factors.

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