scholarly journals Clemastine induces an impairment in developmental myelination

2021 ◽  
Author(s):  
Ana Palma ◽  
Juan Carlos Chara ◽  
Amaia Otxoa-Amezaga ◽  
Anna Planas ◽  
Carlos Matute ◽  
...  

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promising drug with promyelinating properties (Mei et al., 2014). Clemastine penetrates the blood brain barrier efficiently and promotes remyelination in different animal models of neurodegeneration including multiple sclerosis, ischemia and Alzheimer's disease. However, its role in myelination during development is unknown. We showed that clemastine treatment during development increase oligodendrocyte differentiation in both white and gray matter. However, despite the increase in the number of oligodendrocytes, conduction velocity of myelinated fibers of corpus callosum decreased in clemastine-treated mice. Confocal and electron microscopy showed a reduction in the number of myelinated axons and nodes of Ranvier and a reduction of myelin thickness in corpus callosum. To understand the mechanisms leading to myelin formation impairment in the presence of an excess of myelinating oligodendrocytes, we focused on microglial cells which also express muscarinic M1 receptors. Importantly, the population of CD11c+ microglia cells, necessary for myelination, as well as the levels of insulin growth factor-1 decrease in clemastine-treated mice. Altogether, these data suggest that clemastine impact on myelin development is more complex than previously thought and could be dependent on microglia-oligodendrocyte crosstalk. Further studies are needed to clarify the role of microglia cells on developmental myelination.

2020 ◽  
Vol 46 (5) ◽  
pp. 1172-1181 ◽  
Author(s):  
Kayoko Esaki ◽  
Shabeesh Balan ◽  
Yoshimi Iwayama ◽  
Chie Shimamoto-Mitsuyama ◽  
Yoshio Hirabayashi ◽  
...  

Abstract The disturbed integrity of myelin and white matter, along with dysregulation of the lipid metabolism, may be involved in schizophrenia pathophysiology. Considering the crucial role of sphingolipids in neurodevelopment, particularly in oligodendrocyte differentiation and myelination, we examined the role of sphingolipid dynamics in the pathophysiology of schizophrenia. We performed targeted mass spectrometry-based analysis of sphingolipids from the cortical area and corpus callosum of postmortem brain samples from patients with schizophrenia and controls. We observed lower sphingosine-1-phosphate (S1P) levels, specifically in the corpus callosum of patients with schizophrenia, but not in major depressive disorder or bipolar disorder, when compared with the controls. Patient data and animal studies showed that antipsychotic intake did not contribute to the lowered S1P levels. We also found that lowered S1P levels in the corpus callosum of patients with schizophrenia may stem from the upregulation of genes for S1P-degrading enzymes; higher expression of genes for S1P receptors suggested a potential compensatory mechanism for the lowered S1P levels. A higher ratio of the sum of sphingosine and ceramide to S1P, which can induce apoptosis and cell-cycle arrest, was also observed in the samples of patients with schizophrenia than in controls. These results suggest that an altered S1P metabolism may underlie the deficits in oligodendrocyte differentiation and myelin formation, leading to the structural and molecular abnormalities of white matter reported in schizophrenia. Our findings may pave the way toward a novel therapeutic strategy.


Author(s):  
A. Lawley ◽  
M. R. Pinnel ◽  
A. Pattnaik

As part of a broad program on composite materials, the role of the interface on the micromechanics of deformation of metal-matrix composites is being studied. The approach is to correlate elastic behavior, micro and macroyielding, flow, and fracture behavior with associated structural detail (dislocation substructure, fracture characteristics) and stress-state. This provides an understanding of the mode of deformation from an atomistic viewpoint; a critical evaluation can then be made of existing models of composite behavior based on continuum mechanics. This paper covers the electron microscopy (transmission, fractography, scanning microscopy) of two distinct forms of composite material: conventional fiber-reinforced (aluminum-stainless steel) and directionally solidified eutectic alloys (aluminum-copper). In the former, the interface is in the form of a compound and/or solid solution whereas in directionally solidified alloys, the interface consists of a precise crystallographic boundary between the two constituents of the eutectic.


Author(s):  
Nalin J. Unakar

The increased number of lysosomes as well as the close approximation of lysosomes to the Golgi apparatus in tissue under variety of experimental conditions is commonly observed. These observations suggest Golgi involvement in lysosomal production. The role of the Golgi apparatus in the production of lysosomes in mouse liver was studied by electron microscopy of liver following toxic injury by CCI4.


Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.


Author(s):  
L. Tang ◽  
G. Thomas ◽  
M. R. Khan ◽  
S. L. Duan

Cr thin films are often used as underlayers for Co alloy magnetic thin films, such as Co1, CoNi2, and CoNiCr3, for high density longitudinal magnetic recording. It is belived that the role of the Cr underlayer is to control the growth and texture of the Co alloy magnetic thin films, and, then, to increase the in plane coercivity of the films. Although many epitaxial relationship between the Cr underlayer and the magnetic films, such as ﹛1010﹜Co/ {110﹜Cr4, ﹛2110﹜Co/ ﹛001﹜Cr5, ﹛0002﹜Co/﹛110﹜Cr6, have been suggested and appear to be related to the Cr thickness, the texture of the Cr underlayer itself is still not understood very well. In this study, the texture of a 2000 Å thick Cr underlayer on Nip/Al substrate for thin films of (Co75Ni25)1-xTix dc-sputtered with - 200 V substrate bias is investigated by electron microscopy.


Author(s):  
J. R. Michael ◽  
A. D. Romig ◽  
D. R. Frear

Al with additions of Cu is commonly used as the conductor metallizations for integrated circuits, the Cu being added since it improves resistance to electromigration failure. As linewidths decrease to submicrometer dimensions, the current density carried by the interconnect increases dramatically and the probability of electromigration failure increases. To increase the robustness of the interconnect lines to this failure mode, an understanding of the mechanism by which Cu improves resistance to electromigration is needed. A number of theories have been proposed to account for role of Cu on electromigration behavior and many of the theories are dependent of the elemental Cu distribution in the interconnect line. However, there is an incomplete understanding of the distribution of Cu within the Al interconnect as a function of thermal history. In order to understand the role of Cu in reducing electromigration failures better, it is important to characterize the Cu distribution within the microstructure of the Al-Cu metallization.


Author(s):  
Douglas William Jones

Within the past 20 years, archaeobotanical research in the Eastern United States has documented an early agricultural complex before the dominance of the Mesoamerican domesticates (corn, beans, and squash) in late prehistoric and historic agricultural systems. This early agricultural complex consisted of domesticated plants such as Iva annua var.macrocarpa (Sumpweed or Marshelder), Hellanthus annuus (Sunflower) and Chenopodium berlandieri, (Goosefoot or Lasbsquarters), and heavily utilized plants such as Polygonum erectum (Erect Knotweed), Phalaris caroliniana (May grass), and Hordeum pusillum (Little Barley).Recent research involving the use of Scanning Electron Microscopy (SEM) specifically on Chenopodium has established diagnostic traits of wild and domesticated species seeds. This is important because carbonized or uncarbonized seeds are the most commonly recovered Chenopodium material from archaeological sites. The diagnostic seed traits assist archaeobotanists in identification of Chenopodium remains and provide a basis for evaluation of Chenopodium utilization in a culture's subsistence patterns. With the aid of SEM, an analysis of Chenopodium remains from three Late Prehistoric sites in Northwest Iowa (Blood Run [Oneota culture], Brewster [Mill Creek culture], and Chan-Ya-Ta [Mill Creek culture]) has been conducted to: 1) attempt seed identification to a species level, 2) evaluate the traits of the seeds for classification as either wild or domesticated, and 3) evaluate the role of Chenopodium utilization in both the Oneota and Mill Creek cultures.


Author(s):  
C. Ewins ◽  
J.R. Fryer

The preparation of thin films of organic molecules is currently receiving much attention because of the need to produce good quality thin films for molecular electronics. We have produced thin films of the polycyclic aromatic, perylene C10H12 by evaporation under high vacuum onto a potassium chloride (KCl) substrate. The role of substrate temperature in determining the morphology and crystallography of the films was then investigated by transmission electron microscopy (TEM).The substrate studied was the (001) face of a freshly cleaved crystal of KCl. The temperature of the KCl was controlled by an electric heater or a cold finger. The KCl was heated to 200°C under a vacuum of 10-6 torr and allowed to cool to the desired temperature. The perylene was then evaporated over a period of one minute from a molybdenum boat at a distance of 10cm from the KCl. The perylene thin film was then backed with an amorphous layer of carbon and floated onto copper microscope grids.


Author(s):  
J.E. Johnson

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).


Author(s):  
Alan N. Hodgson

The hermaphrodite duct of pulmonate snails connects the ovotestis to the fertilization pouch. The duct is typically divided into three zones; aproximal duct which leaves the ovotestis, the middle duct (seminal vesicle) and the distal ovotestis duct. The seminal vesicle forms the major portion of the duct and is thought to store sperm prior to copulation. In addition the duct may also play a role in sperm maturation and degredation. Although the structure of the seminal vesicle has been described for a number of snails at the light microscope level there appear to be only two descriptions of the ultrastructure of this tissue. Clearly if the role of the hermaphrodite duct in the reproductive biology of pulmonatesis to be understood, knowledge of its fine structure is required.Hermaphrodite ducts, both containing and lacking sperm, of species of the terrestrial pulmonate genera Sphincterochila, Levantina, and Helix and the marine pulmonate genus Siphonaria were prepared for transmission electron microscopy by standard techniques.


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