scholarly journals Developmental axon regrowth and primary neuron sprouting utilize distinct actin elongation factors

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Shiri P. Yaniv ◽  
Hagar Meltzer ◽  
Idan Alyagor ◽  
Oren Schuldiner
Keyword(s):  
Neurite Growth ◽  
Growth Potential ◽  
Neuronal Regeneration ◽  
Cell Type ◽  
Elongation Factors ◽  
Dynamic Expression ◽  
Unique System

Intrinsic neurite growth potential is a key determinant of neuronal regeneration efficiency following injury. The stereotypical remodeling of Drosophila γ-neurons includes developmental regrowth of pruned axons to form adult specific connections, thereby offering a unique system to uncover growth potential regulators. Motivated by the dynamic expression in remodeling γ-neurons, we focus here on the role of actin elongation factors as potential regulators of developmental axon regrowth. We found that regrowth in vivo requires the actin elongation factors Ena and profilin, but not the formins that are expressed in γ-neurons. In contrast, primary γ-neuron sprouting in vitro requires profilin and the formin DAAM, but not Ena. Furthermore, we demonstrate that DAAM can compensate for the loss of Ena in vivo. Similarly, DAAM mutants express invariably high levels of Ena in vitro. Thus, we show that different linear actin elongation factors function in distinct contexts even within the same cell type and that they can partially compensate for each other.

Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanol-induced neurodegeneration

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gleb Nikolaevich Zyuz’kov ◽  
Larisa Arkad`evna Miroshnichenko ◽  
Elena Vladislavovna Simanina ◽  
Larisa Alexandrovna Stavrova ◽  
Tatyana Yur`evna Polykova
Keyword(s):  
Stem Cells ◽  
Alcohol Abuse ◽  
Intracellular Signaling ◽  
Signaling Molecules ◽  
Growth Potential ◽  
Nerve Tissue ◽  
Intracellular Signaling Molecules

Abstract Objectives The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo. Methods In vitro, the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied. To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used. Results Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed. It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways. Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors. It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy). Conclusions The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Dynamic CCN3 expression in the murine CNS does not confer essential roles in myelination or remyelination

2020 ◽  
Vol 117 (30) ◽  
pp. 18018-18028
Author(s):  
Nira de la Vega Gallardo ◽  
Rosana Penalva ◽  
Marie Dittmer ◽  
Michelle Naughton ◽  
John Falconer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Ex Vivo ◽  
Matricellular Protein ◽  
Suprachiasmatic Nuclei ◽  
Dynamic Expression ◽  
Ccn3 Expression ◽  
Cns Myelination

CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3−/−mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.

CNS Myelin: Does a Stabilizing Role in Neurodevelopment Result in Inhibition of Neuronal Repair after Adult Injury?

1998 ◽  
Vol 4 (4) ◽  
pp. 273-284 ◽  
Author(s):  
H. S. Keirstead ◽  
John D. Steeves
Keyword(s):  
Neural Development ◽  
Neurite Growth ◽  
In Vivo Studies ◽  
Inhibitory Effects ◽  
Axonal Plasticity ◽  
Collateral Sprouting ◽  
Axonal Connections

The inhibitory properties of mature oligodendrocytes and CNS myelin for neurite outgrowth were clearly documented more than a decade ago in studies involving co-cultures of dissociated glial cells and neurons. Since then, in vitro and in vivo studies have begun to characterize some of the CNS myelin-associated inhibitors of neurite growth. Furthermore, experimental techniques for neutralizing or suppressing these inhibitory effects have been developed. The results of several experiments, involving the suppression of myelination in the developing or adult CNS, suggest that the relatively late appearance of CNS myelin during neural development may serve to stabilize and restrict axonal outgrowth (e.g., collateral sprouting) after appropriate axonal connections have been established. This suggested developmental role of myelin may consolidate and limit the degree of axonal plasticity within the adult CNS; consequently, however, it might also limit axonal regeneration after injury.

scholarly journals Prospects for the Use of NF-кb Inhibitors to Stimulate the Functions of Regeneration-Competent Cells of Nerve Tissue and Neuroregeneration in Ethanol-Induced Neurodegeneration

2020 ◽  
Vol 11 (1) ◽  
pp. 8065-8074
Keyword(s):  
Intracellular Signaling ◽  
Alcohol Intoxication ◽  
Growth Potential ◽  
Nerve Tissue ◽  
Competent Cells ◽  
Pharmacological Targets ◽  
Intracellular Signaling Molecules

The implementation of the concept of drug therapy of neurological disorders in chronic alcohol intoxication is, in some cases, unsuccessful. Promising is the search for new pharmacological targets among the intracellular signaling molecules of regenerating-competent cells. In the conditions of in vitro and in vivo modeling of ethanol-induced neurodegeneration, the role of NF-кВ in the realization of the growth potential of neural progenitors and the secretion of neurotrophins by glial elements was studied. The absence of participation of NF-кВ in the regulation of mitotic activity of neural SC (NSC) and of neuronal-committed progenitors (NCP) in their optimal living conditions and in the influence of ethanol in vitro is shown. At the same time, NF-кВ hinders the implementation of the NSC specialization process. The prolonged introduction of ethanol per os mice was accompanied by the appearance of an inhibitory value in NF-кВ in relation to the intensity of progenitors proliferation. The blockade of NF-кВ of NSC and NCP animals with neurodegeneration caused the progression of their cell cycle. The participation of NF-кВ in the secretory function of astrocytes and oligodendrogliocytes has been established. The inactivation of the nuclear transcription factor led to a decrease in their production of neurotrophins, including in the case of ethanol. At the same time, there were no changes from the microglia functioning.

scholarly journals Neurocan Is Dispensable for Brain Development

2001 ◽  
Vol 21 (17) ◽  
pp. 5970-5978 ◽  
Author(s):  
Xiao-Hong Zhou ◽  
Cord Brakebusch ◽  
Henry Matthies ◽  
Toshitaka Oohashi ◽  
Emilio Hirsch ◽  
...  
Keyword(s):  
Brain Development ◽  
Late Phase ◽  
Neurite Growth ◽  
Long Term Potentiation ◽  
Brain Anatomy ◽  
Term Potentiation

ABSTRACT Neurocan is a component of the extracellular matrix in brain. Due to its inhibition of neuronal adhesion and outgrowth in vitro and its expression pattern in vivo it was suggested to play an important role in axon guidance and neurite growth. To study the role of neurocan in brain development we generated neurocan-deficient mice by targeted disruption of the neurocan gene. These mice are viable and fertile and have no obvious deficits in reproduction and general performance. Brain anatomy, morphology, and ultrastructure are similar to those of wild-type mice. Perineuronal nets surrounding neurons appear largely normal. Mild deficits in synaptic plasticity may exist, as maintenance of late-phase hippocampal long-term potentiation is reduced. These data indicate that neurocan has either a redundant or a more subtle function in the development of the brain.

scholarly journals Beyond Self-Recycling: Cell-Specific Role of Autophagy in Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 625
Author(s):  
James M. Henderson ◽  
Christian Weber ◽  
Donato Santovito
Keyword(s):  
Cell Types ◽  
Chronic Inflammatory Disease ◽  
In Vivo Studies ◽  
Cell Type ◽  
Therapeutic Implications ◽  
Atherosclerosis Development ◽  
Specific Deletion

Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and underlies the development of cardiovascular diseases, such as myocardial infarction and ischemic stroke. As such, atherosclerosis stands as the leading cause of death and disability worldwide and intensive scientific efforts are made to investigate its complex pathophysiology, which involves the deregulation of crucial intracellular pathways and intricate interactions between diverse cell types. A growing body of evidence, including in vitro and in vivo studies involving cell-specific deletion of autophagy-related genes (ATGs), has unveiled the mechanistic relevance of cell-specific (endothelial, smooth-muscle, and myeloid cells) defective autophagy in the processes of atherogenesis. In this review, we underscore the recent insights on autophagy’s cell-type-dependent role in atherosclerosis development and progression, featuring the relevance of canonical catabolic functions and emerging noncanonical mechanisms, and highlighting the potential therapeutic implications for prevention and treatment of atherosclerosis and its complications.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Anti-obesity role of Aster glehni extract: in vivo and in vitro effects

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  
In Vitro Effects
Sign in / Sign up

Export Citation Format

Share Document