scholarly journals Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival

2008 ◽  
Vol 181 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Philip Van Damme ◽  
Annelies Van Hoecke ◽  
Diether Lambrechts ◽  
Peter Vanacker ◽  
Elke Bogaert ◽  
...  
Keyword(s):  
Nervous System ◽  
Neurite Outgrowth ◽  
Neurotrophic Factor ◽  
Neuronal Survival ◽  
Cultured Neurons ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Protein Levels ◽  
The Central Nervous System ◽  
Enhance Neurite Outgrowth

Recently, mutations in the progranulin (PGRN) gene were found to cause familial and apparently sporadic frontotemporal lobe dementia (FTLD). Moreover, missense changes in PGRN were identified in patients with motor neuron degeneration, a condition that is related to FTLD. Most mutations identified in patients with FTLD until now have been null mutations. However, it remains unknown whether PGRN protein levels are reduced in the central nervous system from such patients. The effects of PGRN on neurons also remain to be established. We report that PGRN levels are reduced in the cerebrospinal fluid from FTLD patients carrying a PGRN mutation. We observe that PGRN and GRN E (one of the proteolytic fragments of PGRN) promote neuronal survival and enhance neurite outgrowth in cultured neurons. These results demonstrate that PGRN/GRN is a neurotrophic factor with activities that may be involved in the development of the nervous system and in neurodegeneration.

scholarly journals NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Paige B. Martin ◽  
Yu Kigoshi-Tansho ◽  
Roger B. Sher ◽  
Gianina Ravenscroft ◽  
Jennifer E. Stauffer ◽  
...  
Keyword(s):  
Quality Control ◽  
Nervous System ◽  
Mouse Models ◽  
Human Disease ◽  
Neuromuscular Disease ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Motor Neuron Degeneration ◽  
Neuron Degeneration ◽  
Ribosome Stalling

Abstract A hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized protein quality control pathway—Ribosome-associated Quality Control (RQC)—by mediating proteolytic targeting of incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to neurodegeneration in mice. Whether neurodegeneration results from defective RQC and whether defective RQC contributes to human disease have remained unknown. Here we show that three independently-generated mouse models with mutations in a different component of the RQC complex, NEMF/Rqc2, develop progressive motor neuron degeneration. Equivalent mutations in yeast Rqc2 selectively interfere with its ability to modify aberrant translation products with C-terminal tails which assist with RQC-mediated protein degradation, suggesting a pathomechanism. Finally, we identify NEMF mutations expected to interfere with function in patients from seven families presenting juvenile neuromuscular disease. These uncover NEMF’s role in translational homeostasis in the nervous system and implicate RQC dysfunction in causing neurodegeneration.

Acute Disseminated Encephalomyelitis

2012 ◽  
Vol 27 (11) ◽  
pp. 1408-1425 ◽  
Author(s):  
Gulay Alper
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Disseminated Encephalomyelitis ◽  
Protein Levels ◽  
Demyelinating Disorder ◽  
Immune Mediated ◽  
Elevated Protein ◽  
Demyelinating Lesions ◽  
Diagnostic Difficulties ◽  
The Central Nervous System

Acute disseminated encephalomyelitis is an immune-mediated inflammatory and demyelinating disorder of the central nervous system, commonly preceded by an infection. It principally involves the white matter tracts of the cerebral hemispheres, brainstem, optic nerves, and spinal cord. Acute disseminated encephalomyelitis mainly affects children. Clinically, patients present with multifocal neurologic abnormalities reflecting the widespread involvement in central nervous system. Cerebrospinal fluid may be normal or may show a mild pleocytosis with or without elevated protein levels. Magnetic resonance image (MRI) shows multiple demyelinating lesions. The diagnosis of acute disseminated encephalomyelitis requires both multifocal involvement and encephalopathy by consensus criteria. Acute disseminated encephalomyelitis typically has a monophasic course with a favorable prognosis. Multiphasic forms have been reported, resulting in diagnostic difficulties in distinguishing these cases from multiple sclerosis. In addition, many inflammatory disorders may have a similar presentation with frequent occurrence of encephalopathy and should be considered in the differential diagnosis of acute disseminated encephalomyelitis.

scholarly journals Automated Analysis of Neurite Outgrowth in Mouse Retinal Explants

2012 ◽  
Vol 18 (5) ◽  
pp. 534-543 ◽  
Author(s):  
Djoere Gaublomme ◽  
Tom Buyens ◽  
Lieve Moons
Keyword(s):  
Neurite Outgrowth ◽  
Neurotrophic Factor ◽  
Automated Analysis ◽  
Explant Culture ◽  
Culture Technique ◽  
Local Thresholding ◽  
Retinal Explants ◽  
The Central Nervous System ◽  
Manual Methods

Despite intensive research efforts over the past years, regeneration of injured axons in the central nervous system remains elusive. In the quest for neurostimulatory agents that promote regeneration, well-defined models and analysis methods are required. Tissue explant cultures closely resemble the in vivo situation, making them ideal to study the effect of compounds on the neuro-glial network. This study reports the optimization of an explant culture technique using retinas of neonatal mice and the development of an analysis script that allows for rapid and automated analysis of neurite outgrowth from these explants. The key features of this script (i.e., local thresholding and form selection) allow for swift and unbiased detection of neurite outgrowth. The novel analysis method is compared with two commonly used manual methods and successfully validated by performing dose-response studies with molecules known to either inhibit (anti–β1-integrin antibody) or stimulate (brain-derived neurotrophic factor and ciliary neurotrophic factor) neurite outgrowth from retinal explants. Finally, the new analysis script is used to study whether retinal explant origin has any effect on neurite outgrowth.

scholarly journals Activated Human T Cells, B Cells, and Monocytes Produce Brain-derived Neurotrophic Factor In Vitro and in Inflammatory Brain Lesions: A Neuroprotective Role of Inflammation?

1999 ◽  
Vol 189 (5) ◽  
pp. 865-870 ◽  
Author(s):  
Martin Kerschensteiner ◽  
Eike Gallmeier ◽  
Lüder Behrens ◽  
Vivian Vargas Leal ◽  
Thomas Misgeld ◽  
...  
Keyword(s):  
T Cells ◽  
Nervous System ◽  
B Cells ◽  
Neurotrophic Factor ◽  
Neuronal Survival ◽  
Neuroprotective Effect ◽  
Brain Derived Neurotrophic Factor ◽  
Human T Cells ◽  
Inflammatory Infiltrates

Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4+ T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.

scholarly journals CXCL13 levels are more increased in cerebrospinal fluid and plasma of patients with acute infectious than in non-infectious diseases of the central nervous system

2017 ◽  
Vol 25 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Brîndușa Țilea ◽  
Septimiu Voidăzan ◽  
Rodica Bălașa ◽  
Adina Huțanu ◽  
Andrea Fodor
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Infectious Diseases ◽  
Cell Count ◽  
Plasma Levels ◽  
Neurological Diseases ◽  
Protein Levels ◽  
Median Plasma ◽  
The Central Nervous System ◽  
Elisa Technique

Abstract Background: During the acute inflammatory process, the CXCL13 chemokine plays an important role in B cell recruitment within the central nervous system (CNS). Objective: The objective of the study consisted of the evaluation of CXCL13 chemokine cerebral spinal fluid (CSF) and plasma levels in patients with acute infectious and non-infectious neurological diseases correlated with pleocytosis and CSF protein levels. Material and method: This retrospective study was conducted over one year and included 72 patients. Thirty-eight patients (52.8%) suffering from infectious neurological disease, acute viral and bacterial meningitis, meningoencephalitis, and 34 patients (44.2%) diagnosed with non-infectious neurological diseases. CXCL13 chemokine CSF and plasma levels were determined through the ELISA technique with the Human CXCL13/BLC/BCA-1 kit. CSF cell count, glucose and protein levels, along with anti-Borrelia burgdorferi antibodies were monitored using the ELISA technique. Results: CXCL13 chemokine levels in the CSF of patients with acute infectious neurological diseases showed a median value of 23.07 pg/mL, which was significantly higher in comparison with the median value of 11.5 pg/mL of patients with noninfectious neurological diseases (p-0.03). CXCL13 median plasma concentration in patients with infectious neurological diseases was 108.1 pg/mL, in comparison with the second patient category, 50.7 pg/ml (p-0.001). We observed a statistically significant association between CXCL13 concentrations, CSF cell count and proteins. The higher the CXCL13 chemokine level, the more increased the cell count was. Conclusions: CXCL13 levels in the CSF was significantly increased in patients with acute infectious neurological diseases compared with patients with non-infectious diseases. Moreover, CXCL13 chemokine concentration was significantly correlated with the number of cells and proteins in the CSF of patients suffering from neuroinfections.

scholarly journals A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor

2021 ◽  
Author(s):  
Fanny Jaudon ◽  
Martina Albini ◽  
Stefano Ferroni ◽  
Fabio Benfenati ◽  
Fabrizia Cesca
Keyword(s):  
Nervous System ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Embryonic Cells ◽  
Inwardly Rectifying Potassium Channel ◽  
Complex Functions ◽  
The Central Nervous System ◽  
Homeostatic Function ◽  
Neurotrophin Signaling ◽  
Neuronal Physiology

Astroglial cells are key to maintain nervous system homeostasis. Neurotrophins are known for their pleiotropic effects on neuronal physiology, but also exert complex functions onto glial cells. In this work, we investigated: (i) the signaling competence of embryonic and postnatal primary cortical astrocytes exposed to brain-derived neurotrophic factor (BDNF); and (ii) the role of Kinase D interacting substrate (Kidins220), a transmembrane scaffold protein that mediates neurotrophin signaling in neurons, in the astrocyte response to BDNF. We found a shift from a kinase-based response in embryonic cells to a predominantly [Ca2+]i-based response in postnatal cultures associated with the decreased expression of the full-length BDNF receptor TrkB, with a contribution of Kidins220 to the BDNF-activated kinase and [Ca2+]i pathways. Finally, Kidins220 participates in astrocytes’ homeostatic function by controlling the expression of the inwardly rectifying potassium channel (Kir) 4.1 and the metabolic balance of embryonic astrocytes. Overall, our data contribute to the understanding of the complex role played by astrocytes within the central nervous system and identify Kidins220 as a novel actor in the increasing number of pathologies characterized by astrocytic dysfunctions.

scholarly journals Inhibition of Mg2+ Extrusion Attenuates Glutamate Excitotoxicity in Cultured Rat Hippocampal Neurons

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2768
Author(s):  
Yutaka Shindo ◽  
Ryu Yamanaka ◽  
Kohji Hotta ◽  
Kotaro Oka
Keyword(s):  
Nervous System ◽  
Steady State ◽  
Hippocampal Neurons ◽  
Neuronal Survival ◽  
Glutamate Excitotoxicity ◽  
Cellular Energy ◽  
Toxic Concentration ◽  
The Central Nervous System ◽  
Steady State Levels ◽  
High Concentrations

Magnesium plays important roles in the nervous system. An increase in the Mg2+ concentration in cerebrospinal fluid enhances neural functions, while Mg2+ deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg2+ due to the release of Mg2+ from mitochondria, followed by a decrease to below steady-state levels. Since Mg2+ deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg2+ decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg2+ extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg2+ release from mitochondria and Mg2+ extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg2+ concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg2+ regulation in neuronal survival under excitotoxicity.

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