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.