Coexistence of perinatal and adult forms of a glial progenitor cell during development of the rat optic nerve

Development ◽  
1990 ◽  
Vol 109 (3) ◽  
pp. 691-698
Author(s):  
G. Wolswijk ◽  
P.N. Riddle ◽  
M. Noble
Keyword(s):  
Optic Nerve ◽  
Progenitor Cell ◽  
Time Course ◽  
Culture Dish ◽  
Adult Rats ◽  
Cell Cycle Time ◽  
Tissue Culture Dish ◽  
Optic Nerves

We have studied the developmental appearance of the O-2A(adult) progenitor cell, a specific type of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell that we have identified previously in cultures prepared from the optic nerves of adult rats. O-2A(adult) progenitors differ from their counterparts in perinatal animals (O-2A perinatal progenitor cells) in antigenic phenotype, morphology, cell cycle time, rate of migration, time course of differentiation into oligodendrocytes or type-2 astrocytes and sensitivity to the lytic effects of complement in vitro. In the present study, we have found that O-2A(adult) progenitor-like cells first appear in the developing optic nerve approximately 7 days after birth and that by 1 month after birth these cells appear to be the dominant progenitor population in the nerve. However, the perinatal-to-adult transition in progenitor populations is a gradual one and O-2A(adult) and O-2A perinatal progenitors coexist in the optic nerve for 3 weeks or more. In addition, cells derived from optic nerves of P21 rats express characteristic features of O-2adult and O-2A perinatal progenitors for extended periods of growth in the same tissue culture dish. Our results thus indicate that the properties that distinguish these two types of O-2A progenitors from each other are expressed in apparently identical environments. Thus, these cells must either respond to different signals present in the environment, or must respond with markedly different behaviours to the binding of identical signalling molecules.

scholarly journals Regional distribution, developmental changes, and cellular localization of CNTF-mRNA and protein in the rat brain.

1991 ◽  
Vol 115 (2) ◽  
pp. 447-459 ◽  
Author(s):  
K A Stöckli ◽  
L E Lillien ◽  
M Näher-Noé ◽  
G Breitfeld ◽  
R A Hughes ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Olfactory Bulb ◽  
Cellular Localization ◽  
Time Course ◽  
Regional Distribution ◽  
Developmental Expression ◽  
Adult Rats

Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a variety of embryonic neurons in culture. The developmental expression of CNTF occurs clearly after the time period of the physiological cell death of CNTF-responsive neurons. This, together with the sites of expression, excludes CNTF as a target-derived neuronal survival factor, at least in rodents. However, CNTF also participates in the induction of type 2 astrocyte differentiation in vitro. Here we demonstrate that the time course of the expression of CNTF-mRNA and protein in the rat optic nerve (as evaluated by quantitative Northern blot analysis and biological activity, respectively) is compatible with such a glial differentiation function of CNTF in vivo. We also show that the type 2 astrocyte-inducing activity previously demonstrated in optic nerve extract can be precipitated by an antiserum against CNTF. Immunohistochemical analysis of astrocytes in vitro and in vivo demonstrates that the expression of CNTF is confined to a subpopulation of type 1 astrocytes. The olfactory bulb of adult rats has comparably high levels of CNTF to the optic nerve, and here again, CNTF-immunoreactivity is localized in a subpopulation of astrocytes. However, the postnatal expression of CNTF in the olfactory bulb occurs later than in the optic nerve. In other brain regions both CNTF-mRNA and protein levels are much lower.

Identification of an adult-specific glial progenitor cell

Development ◽  
1989 ◽  
Vol 105 (2) ◽  
pp. 387-400 ◽  
Author(s):  
G. Wolswijk ◽  
M. Noble
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Time Course ◽  
Demyelinating Disease ◽  
Adult Brain ◽  
Adult Rats ◽  
Cell Cycle Time ◽  
General Importance ◽  
Glial Progenitor

We have found that glial progenitor cells isolated from the optic nerves of adult rats are fundamentally different from their counterparts in perinatal animals. In our studies on bipotential oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells, we have seen that O-2Aadult progenitor cells can be distinguished from O-2Aperinatal progenitors by their morphology and antigenic phenotype, their much longer cell cycle time (65 h versus 18 h), slower rate of migration rate (4 microns h-1 versus 21 microns h-1), and their time course of differentiation into oligodendrocytes or type-2 astrocytes in vitro (less than or equal to 3 days versus greater than 5 days). At least some of the differences between O-2Aadult and O-2Aperinatal progenitor cells appear to be clearly related to the differing cellular requirements of the adult and perinatal central nervous system (CNS). The properties of the O-2Aadult progenitor cells may make these cells ideally suited for the needs of the adult CNS, where rapid exponential increases in the number of oligodendrocytes and O-2A progenitor cells would be inappropriate. However, the properties of the O-2Aadult progenitor cells are such that they may not be able to replace oligodendrocytes in sufficient numbers to repair extensive or recurrent damage in the adult brain, such as in patients suffering from the human demyelinating disease multiple sclerosis. Moreover, available information about other tissues suggests that the transition from perinatal to adult progenitor cell types may represent a developmental mechanism of general importance.

scholarly journals In vitro analysis of the origin and maintenance of O-2Aadult progenitor cells.

1992 ◽  
Vol 116 (1) ◽  
pp. 167-176 ◽  
Author(s):  
D Wren ◽  
G Wolswijk ◽  
M Noble
Keyword(s):  
Adult Life ◽  
Cell Types ◽  
Adult Rats ◽  
Optic Nerves ◽  
Limited Life ◽  
Old Rats ◽  
Vitro Analysis

We have been studying the differing characteristics of oligodendrocyte-type-2 astrocyte (O-2A) progenitors isolated from optic nerves of perinatal and adult rats. These two cell types display striking differences in their in vitro phenotypes. In addition, the O-2Aperinatal progenitor population appears to have a limited life-span in vivo, while O-2Aadult progenitors appear to be maintained throughout life. O-2Aperinatal progenitors seem to have largely disappeared from the optic nerve by 1 mo after birth, and are not detectable in cultures derived from optic nerves of adult rats. In contrast, O-2Aadult progenitors can first be isolated from optic nerves of 7-d-old rats and are still present in optic nerves of 1-yr-old rats. These observations raise two questions: (a) From what source do O-2Aadult progenitors originate; and (b) how is the O-2Aadult progenitor population maintained in the nerve throughout life? We now provide in vitro evidence indicating that O-2Aadult progenitors are derived directly from a subpopulation of O-2Aperinatal progenitors. We also provide evidence indicating that O-2Aadult progenitors are capable of prolonged self renewal in vitro. In addition, our data suggests that the in vitro generation of oligodendrocytes from O-2Aadult progenitors occurs primarily through asymmetric division and differentiation, in contrast with the self-extinguishing pattern of symmetric division and differentiation displayed by O-2Aperinatal progenitors in vitro. We suggest that O-2Aadult progenitors express at least some properties of stem cells and thus may be able to support the generation of both differentiated progeny cells as well as their own continued replenishment throughout adult life.

Cd(2+)-induced injury in CNS white matter

1996 ◽  
Vol 76 (5) ◽  
pp. 3264-3273 ◽  
Author(s):  
R. Fern ◽  
J. A. Black ◽  
B. R. Ransom ◽  
S. G. Waxman
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Mitochondrial Respiration ◽  
Time Course ◽  
White Matter Injury ◽  
Neurological Injury ◽  
Antimycin A ◽  
Optic Nerves ◽  
Voltage Gated ◽  
Ca2 Channels

1. The affect of extracellular Cd2+ on CNS white matter was studied using an isolated rat optic nerve preparation. A 100-min exposure to 200 microM Cd2+ reduced the area of the compound action potential (CAP) recorded from the optic nerve to 32.6 +/- 3.8% (mean +/- SE) of the preexposure area, compared with a reduction to 74.9 +/- 2.9% after 100 min in control conditions (P > 0.001). This CAP reduction was not reversed after 120 min of reperfusion with Cd(2+)-free solution, or by perfusion with Cd2+ chelators. 2. Cd(2+)-induced CAP loss occurred in the absence of extracellular Ca2+. Increasing extracellular Ca2+ concentration to 16 mM, however, prevented Cd(2+)-induced CAP loss. Once evident, Cd(2+)-induced CAP reduction could not subsequently be reversed by addition of 16 mM Ca2+. 3. Low concentrations of Cd2+ (60 microM) did not significantly reduce CAP area. This concentration of Cd2+ combined with high extracellular K+ (30 mM) caused CAP loss that was blocked by 10 microM nifedipine, an antagonist of L-type voltage-gated Ca2+ channels. 4. Treatment with pharmacological inhibitors of membrane proteins known to be inhibited by Cd2+ did not affect the CAP. These included inhibitors of voltage-gated Ca2+ channels, Ca(2+)-activated K+ channels, Ca(2+)-ATPase and the Na+/Ca2+ exchanger. 5. Treatment with pharmacological agents that inhibit calmodulin or disrupt tubulin, two intracellular proteins affected by Cd2+, did not affect CAP area. 6. The effect of Cd2+ was not prevented by pretreatment with (+)-cyanidanol-3, an agent that prevents Cd(2+)-induced lipid peroxidation. 7. Treatment with antimycin A, a inhibitor of mitochondrial respiration, resulted in irreversible CAP reduction with a time course and extent similar to that produced by 200 microM Cd2+. Cd(2+)-induced CAP reduction was prevented by 1 mM cysteine, which prevents Cd(2+)-induced disruption of mitochondrial respiration. 8. The ultrastructure of optic nerves exposed to 200 microM Cd2+ for 100 min was characterized by swollen mitochondria with disrupted cristae and dissolution of microtubules, which were replaced by flocculent debris. Occasional regions of axonal swelling and empty spaces beneath the myelin also were found. Qualitatively similar changes in mitochondria and cytoskeletal elements were found in optic nerves exposed to antimycin A for 100 min. Astrocytes also displayed disrupted mitochondria and had an electron-lucent appearance under both conditions. 9. The neurological injury produced by exposure to Cd2+ is characterized by lesions of CNS white matter. Our results indicate that Cd(2+)-induced white matter injury in vitro results largely from disruption of mitochondrial respiration after Cd2+ influx through routes that include voltage-gated Ca2+ channels.

Induction of functional cytodifferentiation in the epithelium of tissue recombinants. I. Homotypic seminal vesicle recombinants

Development ◽  
1989 ◽  
Vol 106 (2) ◽  
pp. 219-234 ◽  
Author(s):  
S.J. Higgins ◽  
P. Young ◽  
J.R. Brody ◽  
G.R. Cunha
Keyword(s):  
Seminal Vesicle ◽  
Time Course ◽  
Full Range ◽  
Seminal Vesicles ◽  
Neonatal Rat ◽  
Secretory Proteins ◽  
Functional Variation ◽  
Adult Rats ◽  
Normal Functional

Functional cytodifferentiation of seminal vesicle epithelium was investigated in tissue recombinants. Neonatal rat and mouse seminal vesicles were separated into epithelium and mesenchyme using trypsin. Epithelium and mesenchyme were then recombined in vitro to form interspecific rat/mouse homotypic recombinants. Growth as renal grafts in adult male athymic mice resulted in seminal vesicle morphogenesis in 70% of the recombinants (the remaining 30% failed to grow). Functional cytodifferentiation was judged by the expression of the major androgen-dependent secretory proteins characteristic of the seminal vesicles of adult rats and mice. Antibodies specific for each of these proteins were used to screen tissue sections by immunocytochemistry and to probe protein extracts by immunoblotting techniques. The heterospecific recombinants synthesized the full range of seminal vesicle secretory proteins that typifies the species providing the epithelium of the recombinant, not the mesenchyme. There was little functional variation between individual recombinants. The time course of development corresponded to that of intact neonatal seminal vesicles grown under the same conditions. Morphogenesis and functional cytodifferentiation were not evident after one week, but were well advanced after two weeks. Seminal vesicle recombinants grown for three weeks were indistinguishable morphologically and functionally from normal adult seminal vesicles. In addition, the ability of adult seminal vesicle epithelium to be induced to proliferate was examined. In association with neonatal seminal vesicle mesenchyme, the epithelium of the adult seminal vesicle proliferated and retained its normal functional activity. Thus, seminal vesicle functional cytodifferentiation can be faithfully reproduced in homotypic tissue recombinants. The methods used in this study will be used to investigate seminal vesicle development in instructive inductions of heterotypic epithelia.

scholarly journals Angiotensin type 2 receptor in pancreatic islets of adult rats: a novel insulinotropic mediator

2013 ◽  
Vol 305 (10) ◽  
pp. E1281-E1291 ◽  
Author(s):  
Chunhong Shao ◽  
Irving H. Zucker ◽  
Lie Gao
Keyword(s):  
Pancreatic Islets ◽  
Combined Treatment ◽  
Insulin Biosynthesis ◽  
In Vitro Experiments ◽  
Ang Ii ◽  
Adult Rats ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

In the present study, we evaluated the relative abundance of angiotensin type 2 receptor (AT2R) protein in various tissues of adult rats. We found that pancreatic islets expressed the highest AT2R protein compared with all other tissues. Accordingly, we then determined the functional significance of AT2R in the endocrine pancreas in in vivo and in vitro experiments by using angiotensin II (ANG II) alone, losartan (Los; AT1R antagonist), compound 21 (C21; AT2R agonist), and PD-123319 (PD; AT2R antagonist). Experiments carried out in rats indicated that, 1) ANG II treatment significantly increased plasma insulin concentration (1.51 ± 0.20 vs. 0.82 ± 0.14 ng/ml, n = 7, P < 0.05) in the fed state. This insulinotropic effect was further augmented by combined treatment with ANG II + Los (2.31 ± 0.25 ng/ml, n = 7, P < 0.01). C21 also elevated insulin levels (2.13 ± 0.20 ng/ml, n = 7, P < 0.01), which was completely abolished by PD. 2) ANG II impaired glucose tolerance, whereas ANG II + Los or C21 improved this function. 3) All treated rats displayed an enhanced insulin secretory response to a glucose challenge. 4) All treated rats displayed upregulated proinsulin 2 mRNA and insulin protein expression in the pancreas. In in vitro experiments using INS-1E cells and isolated rat islets, we found that AT2R activation significantly improved insulin biosynthesis and secretion. These results suggest that the AT2R functions as an insulinotropic mediator. AT2R and its downstream signaling pathways may be potential therapeutic targets for diabetes.

scholarly journals Brain extract causes acetylcholine receptor redistribution which mimics some early events at developing neuromuscular junctions.

1982 ◽  
Vol 93 (2) ◽  
pp. 417-425 ◽  
Author(s):  
M M Salpeter ◽  
S Spanton ◽  
K Holley ◽  
T R Podleski
Keyword(s):  
Acetylcholine Receptors ◽  
Neuromuscular Junctions ◽  
Marked Change ◽  
Brain Extract ◽  
Bottom Surface ◽  
Culture Dish ◽  
Tissue Culture Dish ◽  
Em Autoradiography ◽  
Alpha Bungarotoxin

We studied the effect of rat brain extract on rat muscle cells in vitro by light and electron microscope (EM) autoradiography after labeling acetylcholine receptors (AChR's) with 125I-alpha-bungarotoxin. We found that: (a) In the absence of brain extract, peak site densities within AChR clusters usually do not exceed 4,000 sites/micrometer2. (b) Within hours after exposure to brain extract, AChR's redistribute to form clusters in which the peak site densities are greater than 10,000 sites/micrometer2. Receptor concentration within extract-induced clusters is thus within a factor of 2 of that at the neuromuscular junction (nmj). (c) In the absence of extract, the AChR's and AChR clusters are predominantly on the bottom surface of the myotubes (facing the tissue culture dish). After extract treatment, they are predominantly at the top surface. (d) Plasma membrane in regions of high-density AChR clusters is enriched in membrane with enhanced electron density and surface basal lamina whether or not cells are treated with extract. Extract causes an increase in both these specializations on the top surface of the myotubes. (e) Brain extract does not produce an overall increase in AChR site density or a marked change in degradation rate of receptors in either clustered or nonclustered regions. By producing AChR clusters with junctional site densities and enhanced surface specialization, and by causing an overall shift in AChR's distribution, brain extract mimics early events reported at developing neuromuscular junctions.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

scholarly journals Evaluation of the optic nerve using strain and shear wave elastography in patients with multiple sclerosis and healthy subjects

2017 ◽  
Vol 19 (1) ◽  
pp. 39 ◽  
Author(s):  
Mikail İnal ◽  
Sinan Tan ◽  
Erhan M. Yumusak ◽  
Mehmet Hamdi Şahan ◽  
Murat Alpua ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Nerve ◽  
Healthy Volunteers ◽  
Shear Wave ◽  
Healthy Subjects ◽  
Shear Wave Elastography ◽  
Optic Nerves ◽  
Type 3

Aims: Our aim was to evaluate the elasticity features of the optic nerve using strain (SE) and shear wave elastography (SWE) in multiple sclerosis (MS) patients in comparison with healthy subjects. Material and methods: One hundred and seven optic nerves from 54 MS patients and 118 optic nerves from 59 healthy subjects were examined prospectively by SE and SWE. Optic nerves were divided into three types in accordance to the elasticity designs, as follows: type 1 predominantly blue (hardest tissue); type 2 predominantly blue/green (hard tissue); and type 3 predominantly green (intermediate tissue). Quantitative measurements of optic nerve hardness with SWE were analyzed in kilopascals. Results: Elastographic images from healthy volunteers showed mostly type 3 optic nerves (61.9%); type 2 was also found (38.1%), but type 1 was not observed. Elastographic examination of MS patients showed mostly type 2 optic nerves (88%), while some type 1 (4.6%) and type 3 optic nerves (6.5%) were rarely observed. There was a statistically significant difference in terms of elasticity patterns between patients and healthy volunteers (p<0.001). Statistically significant differences were observed between patients and healthy volunteers in the analysis of SWE values (10.381±3.48 kPa and 33.87±11.64 p<0.001). The receiver operating characteristic curve analysis was perfect (0.993; 95% confidence interval [CI]=0.971–0.999), and a cut-off value of 18.3 kPa shear had very high sensitivity and specificity for the patient group. No significant differences were observed between patients with and without previous optic neuritis. Conclusion: SE and SWE examination findings concerning the optic nerve in MS patients demonstrated remarkable differences according to the healthy group.

Cabergoline Stimulates Human Endometrial Stromal Cell Decidualization and Reverses Effects of Interleukin-1β in vitro

2021 ◽  
Author(s):  
Yu Jie ◽  
Sarah L Berga ◽  
Qingying Meng ◽  
Mingjing Xia ◽  
Trudy A Kohout ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Time Course ◽  
Sympathetic Innervation ◽  
Endometrial Stromal Cells ◽  
Catecholaminergic Neurons ◽  
Mrna And Protein Expression

Abstract Context Human embryonic implantation is regulated by neuroendocrine hormones, ovarian steroids, growth factors and cytokines. Sympathetic innervation of the uterus also may play a role. Objective We tested the hypothesis that cabergoline (Cb), an agonist of type 2 dopamine receptors (DRD2), could influence endometrial decidualization in vitro. Design Immunohistochemistry confirmed the presence of catecholaminergic neurons in human uterine tissue. DRD2 mRNA and protein expression in endometrial tissue and cells were validated by quantitative RT-PCR, cDNA microarrays, RNA sequencing and Western blotting. Isolated human endometrial stromal cells (ESC) were subjected to dose-response and time-course experiments in the absence or presence of decidualizing hormones (10 nM estradiol, 100 nM progesterone and 0,5 mM dibutyryl cAMP). In some cases, interleukin (IL)-1β (0.1 nM) was used as an inflammatory stimulus. Well-characterized in vitro biomarkers were quantified. Results DRD2 were maximally expressed in vivo in the mid-secretory phase of the cycle and upregulated in ESC in response to decidualizing hormones, as were classical (eg, prolactin) and emerging (eg, VEGF and connexin 43) differentiation biomarkers. Cabergoline treatment more than doubled decidual biomarker expression, whereas risperidone, a dopamine receptor antagonist, inhibited ESC differentiation by &gt;50%. Cabergoline induced characteristic decidual morphology changes and blocked detrimental effects of IL-1β on decidual cytology. Conclusion Our results support the hypothesis that dopaminergic neurons modulate decidualization in situ. We postulate that dopamine agonists, like Cb, could be developed as therapeutic agents to enhance implantation in couples with inflammation-associated infertility.

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