scholarly journals Pressure-Induced Changes in Astrocyte GFAP, Actin, and Nuclear Morphology in Mouse Optic Nerve

2020 ◽  
Vol 61 (11) ◽  
pp. 14 ◽  
Author(s):  
Yik Tung Tracy Ling ◽  
Mary E. Pease ◽  
Joan L. Jefferys ◽  
Elizabeth C. Kimball ◽  
Harry A. Quigley ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nuclear Morphology ◽  
Induced Changes

Anoxia-induced extracellular ionic changes in CNS white matters: the role of glial cells

1992 ◽  
Vol 70 (S1) ◽  
pp. S181-S189 ◽  
Author(s):  
Bruce R. Ransom ◽  
Daniel M. Philbin Jr.
Keyword(s):  
Optic Nerve ◽  
Glial Cells ◽  
Gray Matter ◽  
Glucose Concentration ◽  
Temporal Association ◽  
Small Magnitude ◽  
Brain White Matter ◽  
Average Maximum ◽  
Ionic Changes ◽  
Induced Changes

The rapid changes in brain extracellular ion concentrations that occur with anoxia are important in understanding the pathophysiology of anoxic – ischemic brain injury. While previous studies have focused on the ionic changes that occur in gray matter areas of the brain, white matter (WM) is also damaged by anoxia. We describe the changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) that accompany anoxia in WM, and present new results indicating that glial cells directly contribute to the observed fluctuations of these ions. Anoxia-induced changes in [K+]o and pHo were measured with ion-selective microelectrodes in the isolated rat optic nerve, a typical WM tract. To assess the contribution of glial cells, recordings were also made in optic nerves that contained only glial cells (produced by neonatal enucleation). Anoxia in WM produced less extreme changes in [K+]o and pHo than are known to occur in gray matter; in WM during anoxia, the average maximum [K+]o was 14 ± 2.9 mM (bath [K+]o = 3 mM) and the average maximum acid shift was 0.31 ± 0.07 pH unit. These extracellular ionic changes were accompanied by rapid shrinkage of extracellular space volume. The ability of optic nerve axons to conduct action potentials was lost in temporal association with the increase in [K+]o. Increasing bath glucose concentration from 10 to 20 mM resulted in a much larger acid shift during anoxia (0.58 ± 0.08 pH unit) and a smaller average increase in [K+]o (9.2 ± 2.6 mM). The increased glucose concentration presumably enhanced anaerobic metabolism, leading to extracellular lactate accumulation and a greater acid shift. More ATP would be available for operation of ion pumps, including the sodium pump, and this would result in less dramatic changes in [K+]o. The optic nerve showed significantly less irreversible damage after 60 min of anoxia in the presence of 20 mM glucose compared with 10 mM glucose. In the pure glial nerve, anoxia caused a 1.2 ± 1.1 mM increase in [K+]o and a 0.10 ± 0.04 unit decline in pHo, with time courses similar to the analogous changes in intact nerves. The small magnitude of these anoxia-induced changes in the glial preparation probably results in part from technical factors having to do with the small size of the pure glial nerves. The magnitude of the changes in the pure glial nerves was influenced by bath glucose concentration, with anoxia in 0 mM glucose producing a 1.7 ± 0.4 mM increase in [K+]o, and a 0.05 ± 0.06 unit decrease in pHo. We conclude that glial cells directly contribute to the ionic changes observed during anoxia in WM.Key words: ions, ischemia, glucose, optic nerve, compound action potential, ion-selective electrodes.

Lesion-induced changes in the expression of ciliary neurotrophic factor and its receptor in rat optic nerve

Glia ◽  
1998 ◽  
Vol 23 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Matthias Kirsch ◽  
Thomas Schneider ◽  
Mun-Yong Lee ◽  
Hans-Dieter Hofmann
Keyword(s):  
Optic Nerve ◽  
Neurotrophic Factor ◽  
Ciliary Neurotrophic Factor ◽  
Induced Changes

Stereological examination of effects of ethanol on optic nerve in experimental alcohol model

2019 ◽  
Vol 38 (5) ◽  
pp. 610-615 ◽  
Author(s):  
T Igit ◽  
N Colcimen
Keyword(s):  
Optic Nerve ◽  
Control Group ◽  
Albino Rats ◽  
Optic Chiasma ◽  
Ethanol Group ◽  
Time Period ◽  
Examination Methods ◽  
Wistar Albino Rats ◽  
Induced Changes ◽  
And Control

The objective of the present study was to perform histological and stereological examination of alcohol-induced changes in the optic nerve, considered an extension of white matter of the brain, in rats. This study included 20 male Wistar albino rats aged 60 days and weighing 190–220 g. The rats were divided into three groups: ethanol ( n = 7), maltodextrin ( n = 7), and control ( n = 6) groups. The ethanol group was administered ethanol at a dose of 6.4% (v/v) instead of water for 18 days; the maltodextrin group received maltodextrin for the same time period, and the control group was the sham group. At the end of the experiment, a 0.5-mm long section of the optic nerve starting from the optic chiasma was dissected and examined with routine microscopic histological examination methods. The modified Cavalieri method was used for stereological measurement. Total tissue area ratios were calculated with a point grid provided by the Shtereom 1.5 software package. The statistical comparison of the groups revealed that the ethanol group had a significant reduction in the number of axons and sheath area of the optic nerve compared to the control and maltodextrin groups ( p < 0.017, p < 0.022, respectively). These results indicate the toxic effects of ethanol on the optic nerve.

scholarly journals Valproic Acid-Induced Changes of 4D Nuclear Morphology in Astrocyte Cells

2020 ◽  
Author(s):  
Alexandr A. Kalinin ◽  
Xinhai Hou ◽  
Alex S. Ade ◽  
Gordon-Victor Fon ◽  
Walter Meixner ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Cellular Reprogramming ◽  
Nuclear Morphology ◽  
Cell Nuclei ◽  
Shape Representations ◽  
Significant Difference ◽  
Shape Irregularity ◽  
Induced Changes ◽  
Primary Human Astrocyte

AbstractHistone deacetylase inhibitors, such as valproic acid (VPA), have important clinical implications as human therapeutics and cellular reprogramming agents. They induce chromatin re-organization associated with changes in cell nuclear morphology. Current approaches aiming to quantify these changes so far have been limited to basic 2D measures. Here, we quantified changes in 3D nuclear morphology of primary human astrocyte cells treated with VPA for 7 days (hence, 4D). We compared volumetric and surface-based 3D shape representations of cell nuclei and selected subset of features that jointly discriminated between normal and treated cells with 85% accuracy on day 7. Over time, VPA-treated nuclear morphologies progressed towards larger size and higher shape irregularity. On day 7, all 11 selected size and shape descriptors demonstrated significant difference between treated and untreated nuclear morphologies, including 22.5% increase in volume and 8.3% reduction in extent (shape regularity) for VPA-treated nuclei. Overall, we showed that 4D surface morphometry accurately characterizes the temporal changes in astrocyte nuclear form that are reflective of the underlying valproate-induced chromatin re-organization. These nuclear structural alterations may serve as a biomarker for histone (de-)acetylation events and provide insights into mechanisms of astrocytes-to-neurons reprogramming.

scholarly journals Anoxia-Induced Changes in Extracellular K+ and pH in Mammalian Central White Matter

1992 ◽  
Vol 12 (4) ◽  
pp. 593-602 ◽  
Author(s):  
Bruce R. Ransom ◽  
Wolfgang Walz ◽  
Peter K. Davis ◽  
Walter G. Carlini
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Action Potential ◽  
Glucose Concentration ◽  
Anaerobic Metabolism ◽  
Compound Action Potential ◽  
Average Maximum ◽  
Ionic Changes ◽  
Induced Changes ◽  
Compound Action

In gray matter (GM), anoxia induces prominent extracellular ionic changes that are important in understanding the pathophysiology of this insult. White matter (WM) is also injured by anoxia but the accompanying changes in extracellular ions have not been studied. To provide such information, the time course and magnitude of anoxia-induced changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) were measured in the isolated rat optic nerve, a representative central WM tract, using ion-selective microelectrodes. Anoxia produced less extreme changes in [K+]o and pHo in WM than are known to occur in GM; in WM during anoxia, the average maximum [K+]o was 14 ± 2.9 m M (bath [K+]o = 3 m M) and the average maximum acid shift was 0.31 ± 0.07 pH unit. The extracellular space volume rapidly decreased by ∼20% during anoxia. Excitability of the rat optic nerve, monitored as the amplitude of the supramaximal compound action potential, was lost in close temporal association with the increase in [K+]o Increasing the bath glucose concentration from 10 to 20 m M resulted in a much larger acid shift during anoxia (0.58 ± 0.08 pH unit) and a smaller average increase in [K+]o (9.2 ± 2.6 m M). The increased extracellular glucose concentration presumably provided more substrate for anaerobic metabolism, resulting in more extracellular lactate accumulation (although not directly measured) and a greater acid shift. Enhanced anaerobic metabolism during anoxia would provide energy for operation of ion pumps, including the sodium pump, that would result in smaller changes in [K+]o. These effects were probably responsible for the observation that the optic nerve showed significantly less damage after 60 min of anoxia in the presence of 20 m M glucose compared to 10 m M glucose. Under normoxic conditions, increasing bath K+ concentration to 30 m M (i.e., well beyond the level shown to occur with anoxia) for 60 min caused abrupt loss of excitability during the period of application but minimal change in the amplitude of the compound action potential following the period of exposure. The anoxia-induced increase in [K+]o, therefore, was not itself directly responsible for irreversible loss of optic nerve function. These observations indicate that major qualitative differences exist between mammalian GM and WM with regard to anoxia-induced extracellular ionic changes.

scholarly journals Developmental and Injury-induced Changes in DNA Methylation in Regenerative versus Non-regenerative Regions of the Vertebrate Central Nervous System

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Sergei Reverdatto ◽  
Aparna Prasad ◽  
Jamie L. Belrose ◽  
Xiang Zhang ◽  
Morgan A. Sammons ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Optic Nerve ◽  
Axon Regeneration ◽  
Chromatin Accessibility ◽  
Cpg Methylation ◽  
Rna Expression ◽  
Cns Injury ◽  
Promoter Regions ◽  
Cord Injury ◽  
Induced Changes

Abstract Background Because some of its CNS neurons (e.g., retinal ganglion cells after optic nerve crush (ONC)) regenerate axons throughout life, whereas others (e.g., hindbrain neurons after spinal cord injury (SCI)) lose this capacity as tadpoles metamorphose into frogs, the South African claw-toed frog, Xenopus laevis, offers unique opportunities for exploring differences between regenerative and non-regenerative responses to CNS injury within the same organism. An earlier, three-way RNA-seq study (frog ONC eye, tadpole SCI hindbrain, frog SCI hindbrain) identified genes that regulate chromatin accessibility among those that were differentially expressed in regenerative vs non-regenerative CNS [11]. The current study used whole genome bisulfite sequencing (WGBS) of DNA collected from these same animals at the peak period of axon regeneration to study the extent to which DNA methylation could potentially underlie differences in chromatin accessibility between regenerative and non-regenerative CNS. Results Consistent with the hypothesis that DNA of regenerative CNS is more accessible than that of non-regenerative CNS, DNA from both the regenerative tadpole hindbrain and frog eye was less methylated than that of the non-regenerative frog hindbrain. Also, consistent with observations of CNS injury in mammals, DNA methylation in non-regenerative frog hindbrain decreased after SCI. However, contrary to expectations that the level of DNA methylation would decrease even further with axotomy in regenerative CNS, DNA methylation in these regions instead increased with injury. Injury-induced differences in CpG methylation in regenerative CNS became especially enriched in gene promoter regions, whereas non-CpG methylation differences were more evenly distributed across promoter regions, intergenic, and intragenic regions. In non-regenerative CNS, tissue-related (i.e., regenerative vs. non-regenerative CNS) and injury-induced decreases in promoter region CpG methylation were significantly correlated with increased RNA expression, but the injury-induced, increased CpG methylation seen in regenerative CNS across promoter regions was not, suggesting it was associated with increased rather than decreased chromatin accessibility. This hypothesis received support from observations that in regenerative CNS, many genes exhibiting increased, injury-induced, promoter-associated CpG-methylation also exhibited increased RNA expression and association with histone markers for active promoters and enhancers. DNA immunoprecipitation for 5hmC in optic nerve regeneration found that the promoter-associated increases seen in CpG methylation were distinct from those exhibiting changes in 5hmC. Conclusions Although seemingly paradoxical, the increased injury-associated DNA methylation seen in regenerative CNS has many parallels in stem cells and cancer. Thus, these axotomy-induced changes in DNA methylation in regenerative CNS provide evidence for a novel epigenetic state favoring successful over unsuccessful CNS axon regeneration. The datasets described in this study should help lay the foundations for future studies of the molecular and cellular mechanisms involved. The insights gained should, in turn, help point the way to novel therapeutic approaches for treating CNS injury in mammals.

scholarly journals Valproic Acid-Induced Changes of 4D Nuclear Morphology in Astrocyte Cells

2021 ◽  
pp. mbc.E20-08-0502
Author(s):  
Alexandr A. Kalinin ◽  
Xinhai Hou ◽  
Alex S. Ade ◽  
Gordon-Victor Fon ◽  
Walter Meixner ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Cellular Reprogramming ◽  
Nuclear Morphology ◽  
Size And Shape ◽  
Induced Changes ◽  
Comprehensive Characterization ◽  
Primary Human Astrocyte ◽  
Over Time

Histone deacetylase inhibitors, such as valproic acid (VPA), have important clinical therapeutic and cellular reprogramming applications. They induce chromatin re-organization that is associated with altered cellular morphology. However, there is a lack of comprehensive characterization of VPA-induced changes of nuclear size and shape. Here, we quantify 3D nuclear morphology of primary human astrocyte cells treated with VPA over time (hence, 4D). We compared volumetric and surface-based representations and identified seven features that jointly discriminate between normal and treated cells with 85% accuracy on day 7. From day 3, treated nuclei were more elongated and flattened and then continued to morphologically diverge from controls over time, becoming larger and more irregular. On day 7, most of the size and shape descriptors demonstrated significant differences between treated and untreated cells, including a 24% increase in volume and 6% reduction in extent (shape regularity) for treated nuclei. Overall, we show that 4D morphometry can capture how chromatin re-organization modulates the size and shape of the nucleus over time. These nuclear structural alterations may serve as a biomarker for histone (de-)acetylation events and provide insights into mechanisms of astrocytes-to-neurons reprogramming.

Sign in / Sign up

Export Citation Format

Share Document