Responses of crayfish neurons and glial cells to photodynamic impact: Intracellular signaling, ultrastructural changes, and neuroglial interactions

2014 ◽  
Vol 8 (1) ◽  
pp. 1-15 ◽  
Author(s):  
A. B. Uzdensky ◽  
M. V. Rudkovskii ◽  
G. M. Fedorenko ◽  
E. V. Berezhnaya ◽  
I. A. Ischenko ◽  
...  
Keyword(s):  
Glial Cells ◽  
Intracellular Signaling ◽  
Ultrastructural Changes ◽  
Neuroglial Interactions

Intracellular Responses of Glial Cells To Monomeric Tau Protein Are Closely Mediated By Heparan Sulfate Proteoglycans (HSPGs)

2021 ◽  
Author(s):  
Liqing Song ◽  
Daniel E. Oseid ◽  
Evan A. Wells ◽  
Troy Coaston ◽  
Anne S Robinson
Keyword(s):  
Gene Expression ◽  
Heparan Sulfate ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Tau Protein ◽  
Intracellular Signaling ◽  
Heparan Sulfate Proteoglycans ◽  
C6 Glioma Cells ◽  
Dependent Manner

Abstract The conversion of soluble tau protein to insoluble, hyperphosphorylated neurofibrillary tangles is a major hallmark leading to neuronal death observed in neurodegenerative tauopathies. Recent work suggests that extracellular, soluble tau binds to negatively charged heparan sulfate proteoglycans (HSPGs) available on the cell surface. In addition, LRP1 has recently been recognized as a major tau receptor, mediating tau uptake and spread. We hypothesized based on this data that monomeric tau would be endocytosed in both an HSPG- and LRP-dependent manner, activating intracellular signaling pathways that would regulate cellular phenotypes. Using live-cell confocal microscopy and flow cytometry, we show that soluble 0N4R monomers were rapidly endocytosed by SH-SY5Y and C6 glioma cells, via actin-dependent macropinocytosis. We also demonstrated the crucial role of HSPGs and LRP1 in cellular endocytosis of monomeric tau by observing reduced tau uptake in C6 glial cells with genetic knockouts of xylosyltransferase-1 – a key enzyme in HSPG synthesis – and LRP1. An ERK1/2 inhibition experiment showed that inhibiting the MEK-ERK1/2 signaling pathway attenuated IL-6 and IL-1β gene expression but not TNF-α . An LRP1 knockdown experiment led to an attenuated propensity for tau uptake and further elevated IL-6 gene expression. Collectively, our data suggest that tau has multiple extracellular binding partners that mediate its internalization through distinct mechanisms. Additionally, this study demonstrates the important role of both HSPG and LRP1 in regulating cellular immune responses to tau protein monomer, which provides a novel target for alleviating the neuroinflammatory environment before the formation of neurofibrillary tangles.

Targeting cAMP-pathway in Regeneration-Competent Cells of Nervous Tissue: Potential to Create a Novel Drug for Treatment of Ethanol-Induced Neurodegeneration

2021 ◽  
Vol 21 ◽  
Author(s):  
Gleb Nikolaevich Zyuz’kov ◽  
Larisa Arkad`evna ◽  
Tatyana Yur`evna Polykova ◽  
Elena Vladislavovna Simanina ◽  
Larisa Alexandrovna Stavrova
Keyword(s):  
Glial Cells ◽  
Intracellular Signaling ◽  
Nervous Tissue ◽  
Adenosine Monophosphate ◽  
Growth Potential ◽  
Microglial Cells ◽  
Camp Pathway ◽  
Competent Cells

Background: Existing neuroprotective drugs are not effective enough to treat alcoholic encephalopathy. This makes the development of novel pharmacological approaches to treating patients with ethanol-induced neurodegeneration(EIN) relevant. Therefore, the search for new targets among intracellular signaling molecules of regeneration-competent cells of nervous tissue is promising. Objective: This study aims to explore the involvement of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the realization of the functions of nervous tissue progenitors and glial cells in EIN. Methods: Experiments were conducted on mice of C57B1/6. EIN was modeled in vitro and in vivo. The effects of the adenylate cyclase (AC) and PKA inhibitors on the colony-forming capacity of neural stem cells (NSC) and neuronal-committed progenitors (NCP), their proliferative activity, and intensity of specialization were investigated. The secretion of neurotrophins by astrocytes, oligodendrocytes, and microglial cells was also evaluated. Individual fractions of cells were obtained using the immunomagnetic separation method. Results: The cAMP/PKA signaling is shown to stimulate the proliferation of the NSC and inhibit the mitotic activity of the NCP under the conditions of their optimal vital activity. cAMP reduces the specialization intensity of both types of progenitors. EIN leads to the inversion of the role of the cAMP/PKA-pathway in the regulation of NSC functions. cAMP-pathway has varying influences on the secretion of neurotrophic growth factors by glial cells depending on their living conditions. AC blockage stimulates the realization of the NSC and NCP growth potential and production of neurotrophins by astrocytes and microglial cells in EIN. Conclusion: These findings show the potential for the use of AC inhibitors as novel effective drugs for the therapy of alcoholic encephalopathy.

scholarly journals Short Chain Fatty Acid Transporter/Receptor Expression and Signaling in Enteric Glial Cells

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1201-1201
Author(s):  
Danielle Defries ◽  
Michelle Beltran
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Glial Cells ◽  
Intracellular Signaling ◽  
Receptor Expression ◽  
Enteric Neurons ◽  
Short Chain ◽  
Monocarboxylate Transporter ◽  
Intestinal Cell ◽  
Enteric Glial Cells

Abstract Objectives The enteric nervous system (ENS) independently coordinates gastrointestinal functions such as motility, secretion, and absorption. Enteric glial cells (EGCs), the largest group of cells within the ENS, secrete neurotrophic factors that support enteric neurons and epithelial growth factors that promote integrity of the intestinal epithelial barrier. Although numerous studies have examined the effect of short chain fatty acids (SCFAs) on functional properties of several intestinal cell types, including enterocytes, enteroendocrine cells, and gut immune cells, no studies to date have examined if and how SCFA influence EGCs. We sought to determine: (1) if EGCs have the capacity to respond to SCFAs; (2) signaling pathways downstream of SCFA transporters/receptors are active in EGCs. Methods Experiments were performed in a stably transformed enteroglial cell line (Ruhl et al., 1998). Cells were treated with propionate (0–10 mM), butyrate (0–5 mM), AR420626 (an FFAR3 agonist), or an FFAR2 agonist. Activation of transporters and receptors was assessed using Western blotting for acetylation and phosphorylation state of proteins downstream of the receptors. Expression of SCFA transporters and receptors was assessed using quantitative PCR. Results Basal expression of monocarboxylate transporter (MCT)-1 and MCT-4, as well as the G-protein coupled receptors FFAR2 and FFAR3 was detected, with expression levels of MCT-1 the highest. GPR109a and Olfr920 were not present in these cells. Butyrate treatment for 2 hours significantly elevated levels of acetylated histone H2B and H3 (P < 0.05), but not histone H2A, suggesting that this SCFA is transported across the plasma membrane to exert intracellular effects. Neither SCFAs nor AR420626 blocked forskolin-induced phosphorylation of protein kinase A (PKA), suggesting that FFAR3 signaling is not active in EGCs. Butyrate, but not the FFAR2 agonist, significantly increased phosphorylation of protein kinase C (PKC) (P < 0.05), suggesting that signaling pathways independent of FFAR2 are triggered by SCFA in EGCs. Conclusions Our preliminary evidence suggests that SCFAs are internalized by EGCs and affect intracellular signaling events. Future studies will determine the implications of histone deacetylation and PKC activation by SCFA on EGC function. Funding Sources University of Winnipeg Major Research Grant.

Insulin-induced exocytosis regulates the cell surface level of low-density lipoprotein-related protein-1 in Müller Glial cells

2018 ◽  
Vol 475 (9) ◽  
pp. 1669-1685 ◽  
Author(s):  
Virginia Actis Dato ◽  
Rubén A. Grosso ◽  
María C. Sánchez ◽  
Claudio M. Fader ◽  
Gustavo A. Chiabrando
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Glial Cells ◽  
Intracellular Signaling ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Rab Gtpases ◽  
Related Protein ◽  
Müller Glial Cells

Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) is expressed in retinal Müller glial cells (MGCs) and regulates intracellular translocation to the plasma membrane (PM) of the membrane proteins involved in cellular motility and activity. Different functions of MGCs may be influenced by insulin, including the removal of extracellular glutamate in the retina. In the present work, we investigated whether insulin promotes LRP1 translocation to the PM in the Müller glial-derived cell line MIO-M1 (human retinal Müller glial cell-derived cell line). We demonstrated that LRP1 is stored in small vesicles containing an approximate size of 100 nm (mean diameter range of 100–120 nm), which were positive for sortilin and VAMP2, and also incorporated GLUT4 when it was transiently transfected. Next, we observed that LRP1 translocation to the PM was promoted by insulin-regulated exocytosis through intracellular activation of the IR/PI3K/Akt axis and Rab-GTPase proteins such as Rab8A and Rab10. In addition, these Rab-GTPases regulated both the constitutive and insulin-induced LRP1 translocation to the PM. Finally, we found that dominant-negative Rab8A and Rab10 mutants impaired insulin-induced intracellular signaling of the IR/PI3K/Akt axis, suggesting that these GTPase proteins as well as the LRP1 level at the cell surface are involved in insulin-induced IR activation.

Changes in the ultrastructure of surviving distal segments of severed axons of the rock lobster.

1998 ◽  
Vol 201 (6) ◽  
pp. 779-791
Author(s):  
I Parnas ◽  
O Shahrabany-Baranes ◽  
N Feinstein ◽  
P Grant ◽  
H Adelsberger ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Confocal Microscopy ◽  
Glial Cells ◽  
Distal Part ◽  
Fluorescent Dye ◽  
Ultrastructural Changes ◽  
Rock Lobster ◽  
Normal Appearance ◽  
Proximal Stump ◽  
Severed Axons

Peripheral axons of lobsters can survive for many months after axotomy. We have investigated the structural and ultrastructural changes seen after axotomy using confocal microscopy and electron microscopy. While the proximal stump had a normal appearance, the distal part of the cut axon became lobulated, and glial cells penetrated the original glial tube (axon tube) in which the axon normally runs. The changes proceeded from the cut end towards the muscle. As time elapsed, the axon tube seemed to be filled with glial cells, but interposed small profiles of the original axon could be identified by injection of a fluorescent dye into the axon. The glial cells send cytoplasmic projections deep into folds of the axolemma, and nuclei were found at the end of these long processes. Proliferation of glial cells was also seen.

scholarly journals Traumatic Brain Injury: Ultrastructural Features in Neuronal Ferroptosis, Glial Cell Activation and Polarization, and Blood–Brain Barrier Breakdown

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1009
Author(s):  
Delong Qin ◽  
Junmin Wang ◽  
Anh Le ◽  
Tom J. Wang ◽  
Xuemei Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Glial Cells ◽  
Cascade Reactions ◽  
Brain Barrier ◽  
Ultrastructural Changes ◽  
Future Research ◽  
Secondary Injury ◽  
Blood Brain

The secondary injury process after traumatic brain injury (TBI) results in motor dysfunction, cognitive and emotional impairment, and poor outcomes. These injury cascades include excitotoxic injury, mitochondrial dysfunction, oxidative stress, ion imbalance, inflammation, and increased vascular permeability. Electron microscopy is an irreplaceable tool to understand the complex pathogenesis of TBI as the secondary injury is usually accompanied by a series of pathologic changes at the ultra-micro level of the brain cells. These changes include the ultrastructural changes in different parts of the neurons (cell body, axon, and synapses), glial cells, and blood–brain barrier, etc. In view of the current difficulties in the treatment of TBI, identifying the changes in subcellular structures can help us better understand the complex pathologic cascade reactions after TBI and improve clinical diagnosis and treatment. The purpose of this review is to summarize and discuss the ultrastructural changes related to neurons (e.g., condensed mitochondrial membrane in ferroptosis), glial cells, and blood–brain barrier in the existing reports of TBI, to deepen the in-depth study of TBI pathomechanism, hoping to provide a future research direction of pathogenesis and treatment, with the ultimate aim of improving the prognosis of patients with TBI.

Glial Connexins and Pannexins in the Healthy and Diseased Brain

2021 ◽  
Vol 101 (1) ◽  
pp. 93-145 ◽  
Author(s):  
Christian Giaume ◽  
Christian C. Naus ◽  
Juan C. Sáez ◽  
Luc Leybaert
Keyword(s):  
Information Processing ◽  
Glial Cells ◽  
Typical Feature ◽  
Therapeutic Strategies ◽  
Membrane Topology ◽  
Gap Junction Channels ◽  
The Past ◽  
Main Cell ◽  
Neuroglial Interactions ◽  
The Brain

Over the past several decades a large amount of data have established that glial cells, the main cell population in the brain, dynamically interact with neurons and thus impact their activity and survival. One typical feature of glia is their marked expression of several connexins, the membrane proteins forming intercellular gap junction channels and hemichannels. Pannexins, which have a tetraspan membrane topology as connexins, are also detected in glial cells. Here, we review the evidence that connexin and pannexin channels are actively involved in dynamic and metabolic neuroglial interactions in physiological as well as in pathological situations. These features of neuroglial interactions open the way to identify novel non-neuronal aspects that allow for a better understanding of behavior and information processing performed by neurons. This will also complement the “neurocentric” view by facilitating the development of glia-targeted therapeutic strategies in brain disease.

scholarly journals LRP1 mediates the IGF-1-induced GLUT1 expression on the cell surface and glucose uptake in Müller glial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Virginia Actis Dato ◽  
María Cecilia Sánchez ◽  
Gustavo Alberto Chiabrando
Keyword(s):  
Glucose Uptake ◽  
Glial Cells ◽  
Intracellular Signaling ◽  
Glucose Transporter ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Dependent Manner ◽  
Müller Glial Cells ◽  
Glut1 Expression ◽  
Signaling Activation

AbstractInsulin-like Growth Factor-1 (IGF-1) is involved in the normal development and survival of retinal cells. Low-density lipoprotein Receptor-related Protein-1 (LRP1) plays a key role on the regulation of several membrane proteins, such as the IGF-1 receptor (IGF-1R). In brain astrocytes, LRP1 interact with IGF-1R and the glucose transporter type 1 (GLUT1), regulating the glucose uptake in these cells. Although GLUT1 is expressed in retinal Müller Glial Cells (MGCs), its regulation is not clear yet. Here, we investigated whether IGF-1 modulates GLUT1 traffic to plasma membrane (PM) and glucose uptake, as well as the involvement of LRP1 in this process in the human Müller glial-derived cell line (MIO-M1). We found that IGF-1 produced GLUT1 translocation to the PM, in a time-dependent manner involving the intracellular signaling activation of MAPK/ERK and PI3K/Akt pathways, and generated a significant glucose uptake. Moreover, we found a molecular association between LRP1 and GLUT1, which was significantly reduced by IGF-1. Finally, cells treated with specific siRNA for LRP1 showed an impaired GLUT1 expression on PM and decreased glucose uptake induced by IGF-1. We conclude that IGF-1 regulates glucose homeostasis in MGCs involving the expression of LRP1.

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