ISDN2014_0202: Role of the neurotrophin receptor p75NTR in GABAergic synapse maturation in neocortex

2015 ◽  
Vol 47 (Part_A) ◽  
pp. 59-59
Author(s):  
Elie Baho ◽  
Bidisha Chattopadhyaya ◽  
Marisol Lavertu Jolin ◽  
Graziella Di Cristo
Keyword(s):  
Neurotrophin Receptor ◽  
Gabaergic Synapse ◽  
Synapse Maturation

scholarly journals A comprehensive p75 neurotrophin receptor gene network and pathway analyses identifying new target genes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Antti Sajanti ◽  
Seán B. Lyne ◽  
Romuald Girard ◽  
Janek Frantzén ◽  
Tomi Rantamäki ◽  
...  
Keyword(s):  
Gene Network ◽  
Brain Plasticity ◽  
Initial Point ◽  
Cellular Damage ◽  
Neurotrophin Receptor ◽  
Signaling Networks ◽  
Network Analyses ◽  
Pathway Analyses ◽  
General Response

Abstract P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred, which makes p75NTR’s related signaling networks an interesting and challenging initial point of investigation. We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n = 235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p < 0.05, false discovery rate corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. These results also identify several genes and their respective protein products as involved in the p75NTR network, which have not previously been clearly studied in this pathway. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in acute brain injuries, neurodegenerative diseases and general response to cellular damage.

scholarly journals Regulation of the p75 neurotrophin receptor attenuates neuroinflammation and stimulates hippocampal neurogenesis in experimental Streptococcus pneumoniae meningitis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dandan Zhang ◽  
Shengnan Zhao ◽  
Zhijie Zhang ◽  
Danfeng Xu ◽  
Di Lian ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Streptococcus Pneumoniae ◽  
Proinflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Hippocampal Neurogenesis ◽  
Clinical Severity ◽  
Neurotrophin Receptor ◽  
Apoptosis And Necrosis

Abstract Background Streptococcus pneumoniae meningitis is a destructive central nervous system (CNS) infection with acute and long-term neurological disorders. Previous studies suggest that p75NTR signaling influences cell survival, apoptosis, and proliferation in brain-injured conditions. However, the role of p75NTR signaling in regulating pneumococcal meningitis (PM)-induced neuroinflammation and altered neurogenesis remains largely to be elucidated. Methods p75NTR signaling activation in the pathological process of PM was assessed. During acute PM, a small-molecule p75NTR modulator LM11A-31 or vehicle was intranasally administered for 3 days prior to S. pneumoniae exposure. At 24 h post-infection, clinical severity, histopathology, astrocytes/microglia activation, neuronal apoptosis and necrosis, inflammation-related transcription factors and proinflammatory cytokines/mediators were evaluated. Additionally, p75NTR was knocked down by the adenovirus-mediated short-hairpin RNA (shRNA) to ascertain the role of p75NTR in PM. During long-term PM, the intranasal administration of LM11A-31 or vehicle was continued for 7 days after successfully establishing the PM model. Dynamic changes in inflammation and hippocampal neurogenesis were assessed. Results Our results revealed that both 24 h (acute) and 7, 14, 28 day (long-term) groups of infected rats showed increased p75NTR expression in the brain. During acute PM, modulation of p75NTR through pretreatment of PM model with LM11A-31 significantly alleviated S. pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal apoptosis and necrosis. Moreover, we found that blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokines/mediators (IL-1β, TNF-α, IL-6 and iNOS). Furthermore, p75NTR knockdown induced significant changes in histopathology and inflammation-related transcription factors expression. Importantly, long-term LM11A-31 treatment accelerated the resolution of PM-induced inflammation and significantly improved hippocampal neurogenesis. Conclusion Our findings suggest that the p75NTR signaling plays an essential role in the pathogenesis of PM. Targeting p75NTR has beneficial effects on PM rats by alleviating neuroinflammation and promoting hippocampal neurogenesis. Thus, the p75NTR signaling may be a potential therapeutic target to improve the outcome of PM.

scholarly journals Regulation of the p75 Neurotrophin Receptor Attenuates Neuroinflammation and Stimulates Hippocampal Neurogenesis in Experimental Streptococcus Pneumoniae Meningitis

2021 ◽  
Author(s):  
Dandan Zhang ◽  
Shengnan Zhao ◽  
Zhijie Zhang ◽  
Danfeng Xu ◽  
Di Lian ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Streptococcus Pneumoniae ◽  
Cell Apoptosis ◽  
Neuronal Cell ◽  
Hippocampal Neurogenesis ◽  
Clinical Severity ◽  
Neurotrophin Receptor ◽  
Double Labeling

Abstract Background: Streptococcus pneumoniae meningitis is a destructive central nervous system (CNS) infection with acute and long-term neurological disorders. Compelling evidence provided by previous studies suggests that p75NTR signaling influences cell survival, apoptosis, and proliferation in brain-injured conditions. However, the role of p75NTR signaling in regulating pneumococcal meningitis (PM)-induced neuroinflammation and altered neurogenesis remains largely to be elucidated.Methods: p75NTR signaling activation in the pathological process of PM was assessed. During acute PM, a small-molecule p75NTR modulator LM11A-31 or vehicle was intranasally administered for 3 days prior to S.pneumoniae exposure. At 24h post-infection, clinical severity, histopathology, astrocytes/microglia activation, neuronal cell apoptosis and death, inflammation-related transcription factors and inflammatory factors were evaluated. Additionally, p75NTR was knocked down by the adenovirus-mediated short-hairpin RNA (shRNA) to ascertain the role of p75NTR in PM. During long-term PM, the intranasal administration of LM11A-31 or vehicle was continued for 7 days after successfully establishing the PM model. Hippocampal neurogenesis was evaluated by double-labeling immunofluorescence with EdU, DCX and NeuN. Results: Our results revealed that both 24h (acute) and 7,14,28day (long-term) groups of infected rats demonstrated increased p75NTR expression in the brain. During acute PM, modulation of p75NTR through pretreatment of PM model with LM11A-31 significantly alleviated S.pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal cell apoptosis and death. Moreover, we found that blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokine (IL-1β, TNF-α, IL-6 and iNOS) in the cortex and hippocampus. Furthermore, p75NTR knockdown induced significant changes in histopathology and inflammation-related transcription factors expression. Importantly, combined LM11A-31 adjuvant therapy significantly improved hippocampal neurogenesis.Conclusion: Our findings suggest that the p75NTR signaling plays an essential role in the pathogenesis of PM. Targeting p75NTR has benefit effects on PM rats by alleviating neuroinflammation and promoting hippocampal neurogenesis. Thus, the p75NTR signaling may be a potential therapeutic target to improve the outcome of PM.

scholarly journals Functional Hallmarks of GABAergic Synapse Maturation and the Diverse Roles of Neurotrophins

2011 ◽  
Vol 5 ◽  
Author(s):  
Rosemarie Grantyn ◽  
Christian Henneberger ◽  
René Jüttner ◽  
Jochen C. Meier ◽  
Sergei Kirischuk
Keyword(s):  
Gabaergic Synapse ◽  
Synapse Maturation

scholarly journals Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

2008 ◽  
Vol 295 (6) ◽  
pp. F1778-F1789 ◽  
Author(s):  
Mary Beth Klinger ◽  
Margaret A. Vizzard
Keyword(s):  
Urinary Bladder ◽  
Intravesical Instillation ◽  
Bladder Function ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Female Rat ◽  
Rat Urinary Bladder ◽  
Micturition Reflex ◽  
Reflex Pathways

Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75NTR), in micturition reflex pathways after cyclophosphamide (CYP)-induced cystitis. p75NTR can bind nerve growth factor (NGF) and modulate NGF-TrkA binding and signaling. We examined p75NTR expression and the role of p75NTR in the micturition reflex in control and CYP-treated rats. p75NTR Immunoreactivity was present throughout the urinary bladder. CYP-induced cystitis (4 h, 48 h, chronic) increased ( P ≤ 0.05) p75NTR expression in whole urinary bladder as shown by Western blotting. The role of p75NTR in bladder function in control and CYP-treated rats was determined using conscious cystometry and immunoneutralization or PD90780, a compound known to specifically block NGF binding to p75NTR. An anti-p75NTR monoclonal antibody or PD90780 was infused intravesically and cystometric parameters were evaluated. Both methods of p75NTR blockade significantly ( P ≤ 0.05) decreased the intercontraction interval and void volume in control and CYP-treated rats. Intravesical infusion of PD90780 also significantly ( P ≤ 0.001) increased intravesical pressure and increased the number of nonvoiding contractions during the filling phase. Control intravesical infusions of isotype-matched IgG and vehicle were without effect. Intravesical instillation of PD90780 significantly ( P ≤ 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75NTR expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75NTR blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75NTR and NGF-TrkA signaling.

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