scholarly journals Axonal mitochondria across species adjust in diameter depending on thickness of surrounding myelin

2019 ◽  
Author(s):  
Benjamin V Ineichen ◽  
Keying Zhu ◽  
Karl E Carlström

AbstractIn the central nervous system (CNS), axons and its surrounding myelin sheaths, generated by oligodendrocytes, greatly depend on each other, where oligodendrocytes provide axons with both trophic and metabolic support. Across spices, assessment of the axon-myelin ultrastructure is the key-approach to visualize de- and re-myelination of axons. However, this assessment omits to provide information on axonal homeostasis or how axon-myelin influence one another. Since mitochondria may adjust in size thus mirroring the intracellular physiological and metabolic status we applied this to myelinated axons in the CNS. We herein show that a large axonal mitochondria diameter correlates with thinner surrounding myelin sheaths across different CNS tracts and species, including human. We also show that the relation between axonal mitochondria diameter and surrounding myelin thickness is a valuable measurement to verify advanced remyelination in two commonly used experimental demyelinating models, namely the cuprizone and the lysolecithin (LPC) model. Lastly, we show that axonal mitochondria adjust in diameter in response to the thickness of the axonal surrounding myelin whereas the opposite adaption was absent. In summary, the link between axonal mitochondria diameter and surrounding myelin thickness provide insight on the axon-myelin relation both during homeostasis and pathological conditions. This link is also translational applicable and can thus contribute to a better understanding on how to study remyelination using experimental models.

1996 ◽  
Vol 54 (2) ◽  
pp. 331-334 ◽  
Author(s):  
L. A. V Peireira ◽  
M. A. Cruz-Höfling ◽  
M. S. J. Dertkigil ◽  
D. L. Graça

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.


2021 ◽  
Vol 15 ◽  
Author(s):  
Davide Marangon ◽  
Nicolò Caporale ◽  
Marta Boccazzi ◽  
Maria P. Abbracchio ◽  
Giuseppe Testa ◽  
...  

Myelin is the lipidic insulating structure enwrapping axons and allowing fast saltatory nerve conduction. In the central nervous system, myelin sheath is the result of the complex packaging of multilamellar extensions of oligodendrocyte (OL) membranes. Before reaching myelinating capabilities, OLs undergo a very precise program of differentiation and maturation that starts from OL precursor cells (OPCs). In the last 20 years, the biology of OPCs and their behavior under pathological conditions have been studied through several experimental models. When co-cultured with neurons, OPCs undergo terminal maturation and produce myelin tracts around axons, allowing to investigate myelination in response to exogenous stimuli in a very simple in vitro system. On the other hand, in vivo models more closely reproducing some of the features of human pathophysiology enabled to assess the consequences of demyelination and the molecular mechanisms of remyelination, and they are often used to validate the effect of pharmacological agents. However, they are very complex, and not suitable for large scale drug discovery screening. Recent advances in cell reprogramming, biophysics and bioengineering have allowed impressive improvements in the methodological approaches to study brain physiology and myelination. Rat and mouse OPCs can be replaced by human OPCs obtained by induced pluripotent stem cells (iPSCs) derived from healthy or diseased individuals, thus offering unprecedented possibilities for personalized disease modeling and treatment. OPCs and neural cells can be also artificially assembled, using 3D-printed culture chambers and biomaterial scaffolds, which allow modeling cell-to-cell interactions in a highly controlled manner. Interestingly, scaffold stiffness can be adopted to reproduce the mechanosensory properties assumed by tissues in physiological or pathological conditions. Moreover, the recent development of iPSC-derived 3D brain cultures, called organoids, has made it possible to study key aspects of embryonic brain development, such as neuronal differentiation, maturation and network formation in temporal dynamics that are inaccessible to traditional in vitro cultures. Despite the huge potential of organoids, their application to myelination studies is still in its infancy. In this review, we shall summarize the novel most relevant experimental approaches and their implications for the identification of remyelinating agents for human diseases such as multiple sclerosis.


Glia ◽  
2018 ◽  
Vol 66 (10) ◽  
pp. 2209-2220 ◽  
Author(s):  
Farrah Blades ◽  
Andrea Aprico ◽  
Rainer Akkermann ◽  
Sarah Ellis ◽  
Michele D. Binder ◽  
...  

1967 ◽  
Vol 34 (2) ◽  
pp. 555-567 ◽  
Author(s):  
Asao Hirano ◽  
Herbert M. Dembitzer

The cerebral white matter of rats subjected to a variety of noxious experimental conditions was examined in the electron microscope. Several unusual configurations of the myelin sheath are identified in addition to the usual configuration. These variations include the presence of (a) formed organelles within the inner and outer loops, (b) isolated islands of cytoplasm in unfused portions of the major dense lines, (c) apparently unconnected cell processes between the sheath and the axon, and (d) concentric, double myelin sheaths. A generalized model of the myelin sheath based on a hypothetical unrolling of the sheath is described. It consists of a shovel-shaped myelin sheet surrounded by a continuous thickened rim of cytoplasm. Most of the unusual myelin configurations are explained as simple variations on this basic theme. With the help of this model, an explanation of the formation of the myelin sheath is offered. This explanation involves the concept that myelin formation can occur at all cytoplasmic areas adjacent to the myelin proper and that adjacent myelin lamellae can move in relation to each other.


2011 ◽  
Vol 1367 ◽  
pp. 22-32 ◽  
Author(s):  
Keisuke Yoshikawa ◽  
Shiro Takei ◽  
Sanae Hasegawa-Ishii ◽  
Yoichi Chiba ◽  
Ayako Furukawa ◽  
...  

1987 ◽  
Vol 83 (1) ◽  
pp. 109-111 ◽  
Author(s):  
C.H. Polman ◽  
C.D. Dijkstra ◽  
C.J.A. de Groot ◽  
J.C. Koetsier ◽  
T. Sminia

Sign in / Sign up

Export Citation Format

Share Document