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

Abstract

Previous work has shown that exposure to exogenous testosterone during synapse elimination permanently stabilizes synapses that would normally be lost in the androgen-sensitive levator ani (LA) muscle, indicating that testosterone is a potent stabilizing factor for developing LA synapses. Terminal Schwann cells (TSCs), which cap the neuromuscular junction, have also been implicated in the control of synaptic stability and may play a decisive role in the selective stabilization of synapses during synapse elimination. In this study, we begin to investigate the possible role of TSCs in the effect of testosterone on synapse elimination by determining whether testosterone influences their number. As the number of TSCs generally correlates with the size of endplates, we also measured endplate size. Male rats were castrated or sham gonadectomized at postnatal day (P) 7 and given capsules containing either testosterone or nothing. Three weeks later (P27–28), LA neuromuscular junctions (NMJs) were stained using immune and nonimmune markers. As expected, testosterone treatment during synapse elimination maintained synapses that would ordinarily be eliminated. In addition, we find that the size of LA endplates and the number of TSCs per LA junction were also increased by the testosterone treatment. However, testosterone significantly increased the number of TSCs on both singly and multiply innervated fibers, indicating that the effect of testosterone on the number of TSCs is not specific to its effect on synapse maintenance. Rather the testosterone-induced increase in the number of TSCs appears related to the size of LA NMJs, a relationship that has precedence.

Steroids and glial cell function

“…Estradiol, progesterone and testosterone enhance Schwann cell proliferation (Jordan and Williams, 2001;Jung-Testas et al, 1993;Lubischer and Bebinger, 1999;Svenningsen and Kanje, 1999) and the proliferation of oligodendrocyte precursors (Ghoumari et al, 2005;Marin-Husstege et al, 2004). In contrast, glucocorticoids decrease proliferation of oligodendrocyte precursors (Alonso, 2000).…”

“…Finally, it should be considered that although steroids may act directly on glial cells in vitro, the final response of glial cells to steroids in vivo is probably influenced by interactions with neurons. For instance, neuronal signals are required for estrogen-mediated induction of progesterone receptor in cultured rat Schwann cells and androgen-receptors expressing neurons probably mediate the effect of androgens on Schwann cell proliferation (Jordan and Williams, 2001) and on the expression of glycoprotein zero (P0) in the sciatic nerve (Magnaghi et al, 1999). Some effects of progesterone on Schwann cells may also be mediated by neuronal progesterone receptors (Chan et al, 2000).…”

Perisynaptic Schwann Cells at the Neuromuscular Synapse: Adaptable, Multitasking Glial Cells

“…It has been shown that there are 3-5 PSC somata in both frog and mammalian mature NMJs, and that the number of PSCs is correlated with the endplate size (Herrera et al 1990;Love and Thompson 1998;Lubischer and Bebinger 1999;Jordan and Williams 2001). It is not clear why PSCs are nonmyelinating even though they can be labeled with antibodies to myelinating glial markers, such as protein zero (P 0 ), myelin-associated glycoprotein (MAG), galactocerebroside, and 2 0 , 3 0 -cyclic nucleotide 3 0 -phosphodiesterase .…”

Synapse-Glia Interactions at the Vertebrate Neuromuscular Junction

“…Schwann cells are present at NMJs soon after initial nerve-muscle contact (Kelly and Zacks 1969;Herrera and others 2000), and the number of these PSCs increases during the first two postnatal weeks, before the phase of rapid synapse growth (Love and Thompson 1998). Moreover, the number of PSCs per endplate is matched to endplate size: their number increases as endplates enlarge and decreases if endplates shrink (Lubischer and Bebinger 1999;Jordan and Williams 2001). More direct evidence of the importance of PSCs comes from knockout mice that lack Schwann cells.…”