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Schwann cells promote synaptogenesis at the neuromuscular junction via transforming growth factor-beta1.

ABSTRACT: Recent studies suggest that glial cells actively participate in the formation, function, maintenance, and repair of the chemical synapse. However, the molecular mechanisms of glia-synapse interactions are largely unknown. We have shown previously that Schwann cell-conditioned medium (SC-CM) promotes synaptogenesis in Xenopus nerve-muscle cocultures. The present study aimed to identify the synaptogenic molecules in SC-CM. Combining biochemical approaches and in vitro bioassays, we found that SC-CM contains transforming growth factor (TGF)-beta1, which is expressed in Schwann cells both in vivo and in vitro. Similar to SC-CM, TGF-beta1 doubled the size of acetylcholine receptor (AChR) clusters at nerve-muscle contacts and significantly increased the percentage of nerve-muscle contacts that show AChR clusters to approximately 60%, compared with approximately 20% seen in control cultures. The synaptogenic effects of SC-CM were abolished if SC-CM was immunodepleted of TGF-beta1 or if the latency-associated protein or a TGF-beta1 receptor kinase inhibitor was added to block the bioactivity of TGF-beta1. Similar to frog SC-CM, mammalian SC-CM also showed synaptogenic effects, which were prevented by immunodepletion of TGF-beta1. TGF-beta1 upregulated agrin expression in spinal neurons, which could explain the increase in AChR clusters in cultures treated with SC-CM. These results suggest that Schwann cells express TGF-beta1, which is both sufficient and necessary for mediating the synapse-promoting effects of Schwann cells at the developing neuromuscular junction. Schwann cell-derived TGF-beta1 thus joins other astrocyte-derived synaptogenic factors in further strengthening the emerging concept that glial cells contribute to synaptogenesis in both the PNS and the CNS.

SUBMITTER: Feng Z

PROVIDER: S-EPMC3844879 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Schwann cells promote synaptogenesis at the neuromuscular junction via transforming growth factor-beta1.

Feng Zhihua Z Ko Chien-Ping CP

The Journal of neuroscience : the official journal of the Society for Neuroscience 20080901 39

Recent studies suggest that glial cells actively participate in the formation, function, maintenance, and repair of the chemical synapse. However, the molecular mechanisms of glia-synapse interactions are largely unknown. We have shown previously that Schwann cell-conditioned medium (SC-CM) promotes synaptogenesis in Xenopus nerve-muscle cocultures. The present study aimed to identify the synaptogenic molecules in SC-CM. Combining biochemical approaches and in vitro bioassays, we found that SC-C ...[more]

PMID: 18815246

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Project description:Terminal Schwann cells are non-myelinating glial cells localized to the neuromuscular junction. They play an important role in regulating many aspects of neuromuscular junction form and function, in health and during disease. However, almost all previous studies of mammalian terminal Schwann cells have used rodent models. Despite a growing awareness of differences in the cellular and molecular anatomy of rodent and human neuromuscular junctions, it remains unclear as to whether these differences also extend to the terminal Schwann cells. Here, we have adapted immunohistochemical protocols to facilitate visualization and comparative morphometric analyses of terminal Schwann cells at the human and mouse neuromuscular junction. We labelled terminal Schwann cells in the peroneus brevis muscle in six adult mice and five humans with antibodies against S100 protein. All human neuromuscular junctions were associated with at least one terminal Schwann cell, consistent with findings from other species, with an average of ∼1.7 terminal Schwann cells per neuromuscular junction in both humans and mice. In contrast, human terminal Schwann cells were significantly smaller than those of mice (P ≤ 0.01), in keeping with differences in overall synaptic size. Human terminal Schwann cell cytoplasm extended significantly beyond the synaptic boundaries of the neuromuscular junction, whereas terminal Schwann cells in mice were largely restricted to the synapse. Moreover, there was a significant difference in the location of terminal Schwann cell nuclei (P ≤ 0.01), with human terminal Schwann cells having their nuclear compartment located beyond the perimeter of the synapse more than the mouse. Taken together, these findings demonstrate that terminal Schwann cells at the human neuromuscular junction have notable differences in their morphology and synaptic relationships compared to mice. These fundamental differences need to be considered when translating the findings of both neuromuscular junction biology and pathology from rodents to humans.

Dataset Information

Schwann cells promote synaptogenesis at the neuromuscular junction via transforming growth factor-beta1.

Publications

Schwann cells promote synaptogenesis at the neuromuscular junction via transforming growth factor-beta1.

Similar Datasets

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