Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection

2007 ◽  
Vol 35 (2) ◽  
pp. 424-427 ◽  
Author(s):  
A. Hennigan ◽  
R.M. O'Callaghan ◽  
Á.M. Kelly
Keyword(s):  
Tyrosine Kinases ◽  
Current Knowledge ◽  
Adult Brain ◽  
Neurotrophin Receptor ◽  
Receptor Subtypes ◽  
P75 Neurotrophin Receptor ◽  
Receptor Kinase ◽  
Dual Roles ◽  
Exercise Induced ◽  
Activity Dependent

It is beyond doubt that the neurotrophin family of proteins plays key roles in determining the fate of the neuron, not only during embryonic development, but also in the adult brain. Neurotrophins such as NGF (nerve growth factor) and BDNF (brain-derived neurotrophic factor) can play dual roles: first, in neuronal survival and death, and, secondly, in activity-dependent plasticity. The neurotrophins manifest their effects by binding to two discrete receptor subtypes: the Trk (tropomyosin receptor kinase) family of RTKs (receptor tyrosine kinases) and the p75NTR (p75 neurotrophin receptor). The differential activation of these receptors by the mature neurotrophins and their precursors, the proneurotrophins, renders analysis of the biological functions of these receptors in the adult brain highly complex. Here, we briefly give a broad review of current knowledge of the roles of neurotrophins in the adult brain, including expression of hippocampal plasticity, neurodegeneration and exercise-induced neuroprotection.

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 An Intracellular Domain Fragment of the p75 Neurotrophin Receptor (p75NTR) Enhances Tropomyosin Receptor Kinase A (TrkA) Receptor Function

2013 ◽  
Vol 288 (16) ◽  
pp. 11144-11154 ◽  
Author(s):  
Dusan Matusica ◽  
Sune Skeldal ◽  
Alex M. Sykes ◽  
Nickless Palstra ◽  
Aanchal Sharma ◽  
...  
Keyword(s):  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Receptor Kinase ◽  
Receptor Function ◽  
Trka Receptor ◽  
Intracellular Domain ◽  
Kinase A

scholarly journals Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L

2019 ◽  
Author(s):  
Christina Chatzi ◽  
Gina Zhang ◽  
William Hendricks ◽  
Yang Chen ◽  
Eric Schnell ◽  
...  
Keyword(s):  
Granule Cells ◽  
Membrane Curvature ◽  
Synaptic Function ◽  
Adult Brain ◽  
Voluntary Exercise ◽  
Excitatory Postsynaptic Currents ◽  
Dentate Granule Cells ◽  
Postsynaptic Currents ◽  
Exercise Induced ◽  
Activity Dependent

AbstractExercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked mature hippocampal dentate granule cells that were specifically activated during exercise using conditional Fos-TRAP mice. Only a few dentate granule cells were active at baseline, but two hours of voluntary exercise markedly increased the number of activated neurons. Activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied gene in the adult brain. Overexpression of Mtss1L in neurons increased spine density, leading us to hypothesize that its I-BAR domain initiated membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.One Sentence SummarySingle episodes of voluntary exercise induced a functional increase in hippocampal synapses mediated by activity-dependent expression of the BAR protein Mtss1L, acting as a novel early effector of synapse formation.

scholarly journals Role of Tyrosine Phosphorylation in The Antioxidant Effects of The P75 Neurotrophin Receptor

2009 ◽  
Vol 2 (4) ◽  
pp. 238-246 ◽  
Author(s):  
Tong Zhang ◽  
Zhiping Mi ◽  
Nina F. Schor
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oxidant Stress ◽  
Cholinergic Neurons ◽  
Adult Brain ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Differential Sensitivity ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor

The p75 neurotrophin receptor (p75NTR) is an α-and γ-secretase substrate expressed preferentially in the cholinergic neurons of the nucleus basalis of Meynert, the hippocampus, and the cerebellum of the adult brain. Mutations of the γ-secretase, presenilin, have been implicated in familial Alzheimer's disease. Furthermore, oxidative and inflammatory injury to the cholinergic neurons of the nucleus basalis of Meynert and hippocampus plays a critical role in the pathology of Alzheimer's disease. The intracellular domain of p75NTR (p75ICD) is the α- and γ-secretase cleavage fragment of the holoreceptor that functions as an antioxidant in PC12 rat pheochromocytoma cells. Phosphorylation of the receptor is thought to be necessary for many of its functions, and two tyrosines in p75ICD have been among the functionally important phosphorylation sites. Site-directed mutagenesis was used to generate three p75ICD mutants that cannot be phosphorylated at either or both tyrosines, respectively. Each of these mutants was expressed in p75NTR-deficient PC12 cells to determine the effects of blocking phosphorylation at specific sites on the antioxidant activity of p75ICD. Interfering with phosphorylation at tyrosine-337 impairs antioxidant function, while interfering with phosphorylation at tyrosine-366 does not, and may in fact impart protection from oxidant stress. Neither MAPK (i.e., p38, ERK1, ERK2) content nor NF-κB activation accounts for the differential sensitivity to oxidant stress among the differentially phosphorylated p75NTR cell lines. However, differences in the time course of ERK1,2 phosphorylation among the lines account in large measure for their differential oxidant sensitivity. The phosphorylation state of specific sites on p75ICD may modulate the resistance of neurons in Alzheimer's disease-relevant brain regions to oxidant stress.

The Effects of P75NTR on Learning Memory Mediated by Hippocampal Apoptosis and Synaptic Plasticity

2020 ◽  
Vol 26 ◽  
Author(s):  
Jun-Jie Tang ◽  
Shuang Feng ◽  
Xing-Dong Chen ◽  
Hua Huang ◽  
Min Mao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Neurological Diseases ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Negative Effects ◽  
Apoptotic Effect ◽  
New Ideas ◽  
The Relationship

: Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its pro-apoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or pro-apoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

Sign in / Sign up

Export Citation Format

Share Document