Regulation of Terminal Schwann Cell Number at the Adult Neuromuscular Junction

Abstract

Terminal Schwann cells (TSCs), neuroglia that cover motoneuron terminals, play a role in regulating the structure and function of the neuromuscular junction. In rats, the number of TSCs at each junction increases rapidly in early postnatal life and more slowly in young adults. It is possible that TSC number increases to match increasing endplate area. Alternatively, the increase in TSC number may reflect a developmental process independent of endplate size or terminal function. To experimentally test the relationship between endplate size and TSC number, we manipulated endplate area in an androgen-sensitive muscle of the rat, the levator ani (LA), by castration and by androgen replacement. We found that TSC number not only increased as endplates enlarged but also decreased when endplates shrank. Ninety days after castration, TSC number decreased by approximately 20% (one cell per junction) as endplate size decreased by 30%. These effects were reversed by testosterone. Testosterone levels did not affect TSC number in the extensor digitorum longus (EDL) muscle, where endplate area was unaffected by castration or testosterone treatment. TSC number was, however, significantly correlated with endplate area in both LA and EDL muscles. Furthermore, the relationship between endplate size and TSC number, as defined by the slope of the regression line, was the same in LA and EDL muscles, indicating that this relationship is not a unique feature of the LA muscle. These data suggest that TSC number is a dynamic property of the neuromuscular synapse that is actively regulated throughout life.

Biology and pathology of nonmyelinating Schwann cells

“…As the junction grows during development and adds active zones and increases the area of the postsynaptic receptors, the tSCs increase in number (Love and Thompson, 1998). There is a rough correlation between the size of the synaptic contact and the number of tSCs (Lubischer and Bebinger, 1999). Interestingly, not only can tSC number increase with increasing size, but it also decreases as muscle fibers and their NMJs atrophy.…”

“…Interestingly, not only can tSC number increase with increasing size, but it also decreases as muscle fibers and their NMJs atrophy. Castration results in atrophy of androgen-sensitive muscles in the rat, and, as the muscle fibers shrink, the number of Schwann cells above their NMJs is reduced (Lubischer and Bebinger, 1999). It is not known if this reduction involves cell death, cell migration, or cell transdetermination.…”

The spinal nucleus of the bulbocavernosus: Firsts in androgen-dependent neural sex differences

“…These anabolic effects of androgens involve changes in perineal muscle fiber size, without a change in fiber number (Venable, 1966). Androgens in adulthood also maintain BC/LA neuromuscular junction size (Bleisch and Harrelson, 1989;Balice-Gordon et al, 1990;Lubischer and Bebinger, 1999), acetylcholine receptor number (Bleisch et al, 1982;Bleisch and Harrelson, 1989), and peripheral nerve activity (Fargo et al, 2003).…”

Testosterone Regulates Terminal Schwann Cell Number and Junctional Size during Developmental Synapse Elimination

“…The NMJs of LA and EDL muscles were visualized using a modified protocol [Lubischer and Bebinger, 1999]. Sections from each muscle were divided into three series and stained to visualize the following components of the NMJ: (1) SCs, axons and nerve terminals ( fig.…”

“…Although junctional size appears to be the predominant factor regulating the number of TSCs throughout the life span [Love and Thompson, 1998;Lubischer and Bebinger, 1999], additional, and as yet unidentified factors also appear to contribute to the regulation of TSC number [Love and Thompson, 1998].…”