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 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.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

scholarly journals FOXO Transcriptional Factors and Long-Term Living

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ghulam Murtaza ◽  
Abida Kalsoom Khan ◽  
Rehana Rashid ◽  
Saiqa Muneer ◽  
Syed Muhammad Farid Hasan ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Healthy Aging ◽  
Growth Stress ◽  
Human Longevity ◽  
Growth Factor Signaling ◽  
Forkhead Box ◽  
Foxo Transcription Factors ◽  
Genetic And Environmental Factors

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity.

scholarly journals Patterns of Local and Systemic Cytokines in Bacterial Meningitis and its Relation with Severity and Long-Term Sequelae

2015 ◽  
Vol 10 ◽  
pp. BMI.S35005 ◽  
Author(s):  
Federico Perdomo-Celis ◽  
Miguel A. Torres ◽  
Henry Ostos ◽  
Javier Gutierrez-Achury ◽  
Victor Molano ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Clinical Severity ◽  
Clinical Role ◽  
Strong Negative Correlation ◽  
Neurological Sequelae ◽  
Flow Cytometric ◽  
Factor Α ◽  
To Receive

Bacterial meningitis (BM) is a pyogenic infection present in the subarachnoid space, potentially fatal and frequently associated with neurological sequelae. During BM, cytokines (CTs) are locally produced. We sought to determine the CTs’ clinical role as disease severity predictors in adults, which is not completely clear. Using a bead-based flow cytometric assay, levels of six CTs were determined in cerebrospinal fluid (CSF) and plasma from 18 adult BM patients and 19 uninfected controls. Long-term neurological sequelae were evaluated using the Glasgow Outcome Scale (GOS). All evaluated CTs were higher in CSF than in plasma, and the levels of CSF interleukin (IL)-6, IL-8, IL-10, IL-1β, and tumor necrosis factor-α and plasma IL-10 and IL-12p70 were significantly higher in patients with severe sepsis than with sepsis, suggesting an association with clinical severity. There was a strong negative correlation between CSF IL-6 and plasma IL-12p70 with GOS score, supporting the possible role of these CTs in the development of neurological long-term sequelae. These findings could be helpful to identify candidates to receive neuroprotective treatments and early physiotherapy schemes.

The protective role of oxymatrine on neuronal cell apoptosis in the hemorrhagic rat brain

2012 ◽  
Vol 143 (1) ◽  
pp. 228-235 ◽  
Author(s):  
Man Huang ◽  
Yue-Yu Hu ◽  
Xiao-Qiao Dong ◽  
Qiu-Ping Xu ◽  
Wen-Hua Yu ◽  
...  
Keyword(s):  
Rat Brain ◽  
Cell Apoptosis ◽  
Neuronal Cell ◽  
Protective Role

Functional role of transcription factors during aβinduced neuronal cell death

2000 ◽  
Vol 21 ◽  
pp. 53
Author(s):  
Robert P. Bowser ◽  
Kelly L. Jordan-Sciutto ◽  
James L. Rhodes
Keyword(s):  
Cell Death ◽  
Transcription Factors ◽  
Functional Role ◽  
Neuronal Cell Death ◽  
Neuronal Cell

Long-term treadmill exercise inhibits neuronal cell apoptosis and reduces tau phosphorylation in the cerebral cortex and hippocampus of aged rats

2017 ◽  
Vol 62 (11) ◽  
pp. 755-757 ◽  
Author(s):  
Guoliang Fang ◽  
Jiexiu Zhao ◽  
Pengfei Li ◽  
Liang Li ◽  
Tao Yu ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cell Apoptosis ◽  
Treadmill Exercise ◽  
Neuronal Cell ◽  
Tau Phosphorylation ◽  
Aged Rats

FoxO3 transcription factor promotes autophagy after oxidative stress injury in HT22 cells

2020 ◽  
Author(s):  
Aiqing Deng ◽  
Limin Ma ◽  
Xueli Zhou ◽  
Xin Wang ◽  
Shouyan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cell Injury ◽  
Cell Damage ◽  
Critical Role ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Stress Injury ◽  
Oxidative Stress Injury

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide (H2O2) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H2O2-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H2O2-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3-Methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on H2O2-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit H2O2-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain.

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