Mechanical injury to the adult mammalian spinal cord results in permanent morphological disintegration including severance/laceration of brain-cord axons at the lesion site. We report here that some of the structural consequences of injury can be averted by altering the cellular components of the lesion site with x-irradiation. We observed that localized irradiation of the unilaterally transected adult rat spinal cord when delivered during a defined time-window (third week) postinjury prevented cavitation, enabled establishment of structural integrity, and resulted in regrowth of severed corticospinal axons through the lesion site and into the distal stump. In addition, we examined the natural course of degeneration and cavitation at the site of lesion with time after injury, noting that through the third week postinjury recovery processes are in progress and only at the fourth week do the destructive processes take over. Our data suggest that the adult mammalian spinal cord has innate mechanisms required for recovery from injury and that timed intervention in certain cellular events by x-irradiation prevents the onset of degeneration and thus enables structural regenerative processes to proceed unhindered. We postulate that a radiation-sensitive subgroup of cells triggers the delayed degenerative processes. The identity of these intrusive cells and the mechanisms for triggering tissue degeneration are still unknown.
Myoblast fusion has been studied in cultures of chick embryonic muscle utilizing ultrastructural techniques. The multinucleated muscle cells (myotubes) are generated by the fusion of two plasma membranes from adjacent cells, apparently by forming a single bilayer that is particle-free in freeze-fracture replicas. This single bilayer subsequently collapses, and cytoplasmic continuity is established between the cells. The fusion between the two plasma membranes appears to take place primarily within particle-free domains (probably phospholipid enriched), and cytoplasmic unilamellar, particle-free vesicles are occasionally associated with these regions. These vesicles structurally resemble phospholipid vesicles (liposomes). They are present in normal myoblasts, but they are absent in certain fusion-arrested myoblast populations, such as those treated with either 5-bromodeoxyuridine (BUdR), cycloheximide (CHX), or phospholipase C (PLC). The unilamellar, particle-free vesicles are present in close proximity to the plasma membranes, and physical contact is observed frequently between the vesicle membrane and the plasma membrane. The regions of vesicle membrane-plasma membrane interaction are characteristically free of intramembrane particles. A model for myoblast fusion is presented that is based on an interpretation of these observations. This model suggests that the cytoplasmic vesicles initiate the generation of particle-depleted membrane domains, both being essential components in the fusion process. KEY WORDS freeze-fracture membrane fusion myoblast fusion myogenesis plasma membranes unilamellar vesiclesThe multinucleated muscle fiber is generated during myogenesis by fusion of mononucleated myoblasts. Several ultrastructural studies (13,21,35,40) provided the basis for the current appreciation of the fusion process: cytoplasmic continuity is established between two fusing myoblasts as a result of the partial disappearance of the plasma membranes. Consequently, many of the studies related to myoblast fusion were focused on the plasma membrane and its involvement in the process; for example, there have been a number of studies on myoblast fusion that have been focused on the cell surface membrane proteins. The rationale for these studies has been that fusion must be regulated and carried out by cell surface membrane components, and the obvious candidate is a protein or group of proteins (3,5,9,11,24,35,36,39). Moreover, two processes that may be fundamentally different-(a) recognition between cells and (b) membrane fusionhave not been distinguished in most of these studies. These two processes occur independently in a wide variety of cellular systems; for example, recognition may be an important process in many differentiating multicellular systems where membrane fusion is not a consequence (23). Con-J. CELL BIOLO6Y 9 The Rockefeller University Press.
Cell-to-cell communication was characterized in prefusion chick embryo myoblast cultures, and it was determined that the prefusion myoblasts can interact via gap junctions, ionic coupling, and metabolic coupling. The biological relevance of this communication was supported by the detection of gap junctions between myoblasts in embryonic muscle. Communication was also examined in fusionarrested cultures to determine its potential relationship to fusion competency. In cultures that were fusion arrested by treatment with either 1.8 mM ethyleneglycolbis-(fl-aminoethyl ether)N,N'-tetraacetic acid (EGTA), 3.3 x 10 -6 M 5-bromodeoxyuridine (BUdR), or 1 /~g/ml cycloheximide (CHX), both gap junctions and ionic coupling were present. Therefore, it is possible to conclude that cell communication is not a sufficient property by itself, to generate fusion between myoblasts. The potential role of communication in myogenesis is discussed with respect to these observations. KEY WORDS cell-to-cell communication junctions 9 ionic coupling metabolic coupling myoblast fusion myogenesis gapThe differentiation of skeletal muscle in vivo and in vitro (in culture) is accompanied by the fusion of mononucleated muscle cells (myoblasts) into multinucleated mature muscle fibers (58). This fusion event, in culture, is preceded by a period of cell multiplication and cellular interaction. During this time, the cells are closely apposed and aligned in multicellular strings; this stage of differentiation has been referred to as the "prefusion lag period" (61). Under standard culture conditions this lag period is quite constant, and only cells which have completed their prefusion changes participate in the formation of muitinucleated fibers (59). The fusion process that follows the lag period has been previously regarded as a critical event in myogenesis. However, at present, it appears that it is just one of the important events that contribute to the formation of a differentiated muscle fiber (1, 12. 16, 19, 26, 31, 34, 36, 41, 54, 55, 56, 57, 62). The actual fusion process requires a direct physical interaction of the plasma membranes from adjacent cells, and this had led to a series of investigations of the cell surface elements that may be involved in regulating fusion (5,14,20). Other studies have suggested that fusion is not necessarily regulated by cell surface components; it may, in fact, be under the direct control of intracellular elements (62). Recently, it has been reported that a specific type of cell contact, the gap junction (30), and low-resistance pathways (6) are present between muscle cells during amphibian myotome development in vivo. In both studies, it was suggested that gap junctional communication between the muscle cells is related to the efficient transfer of excitatory stimuli from somite to somite, and not to cell fusion. Data from studies on embryonic rat and chick skeletal muscle cells in culture indicate the possible existence of ionic coupling (measured indirectly) and gap junctionlike structures betwee...
Neurobiology. In the article ''Severed corticospinal axons recover electrophysiologic control of muscle activity after x-ray therapy in lesioned adult spinal cord'' by Nurit Kalderon and Zvi Fuks, which appeared in number 20, October 1, 1996, of Proc. Natl. Acad. Sci. USA (93, 11185-11190), the following correction should be noted. Due to a printer's error, Fig. 5 was unsatisfactorily reproduced and a better version appears below. FIG. 5. The morphological features of the lesion site in two lesioned cords, unirradiated (a-e) and irradiated (Xa-Xe), obtained from the rats whose EMG recordings are shown in Fig. 3B and Fig. 3C, respectively. Serial reconstruction of the two cords are shown; each panel is a composite of thionin-stained horizontal sections taken from different regions along the dorsal-ventral direction. Indicated are the left (L) and the right (R) hemicords, the extent of incision traversing from left (clear arrow) past the midline and into the right hemicord (arrowhead), and the dorsal nerves (asterisks). Note in the untreated cord the cavitation and tissue degeneration throughout the entire volume surrounding the incision site. In the irradiated cord the incision disappeared and an almost complete structural continuity was established. (Bar ϭ 1 mm.) CorrectionProc. Natl. Acad. Sci. USA 93 (1996) Communicated by Joshua Lederberg, The Rockefeller University, New York, NY July 9, 1996 (received for review February 21, 1996) ABSTRACT Mechanical injury to the adult mammalian spinal cord results in permanent loss of structural integrity at the lesion site and of the brain-controlled function distal to the lesion. Some of these consequences were permanently averted by altering the cellular constituents at the lesion site with x-irradiation delivered within a critical time window after injury. We have reported in a separate article that xirradiation of sectioned adult rat spinal cord resulted in restitution of structural continuity and regrowth of severed corticospinal axons across and deep into the distal stump. Here, we report that after x-ray therapy of the lesion site severed corticospinal axons of transected adult rat spinal cord recover electrophysiologic control of activity of hindlimb muscles innervated by motoneurons distal to the lesion. The
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.