Perisynaptic schwann cells

Perisynaptic schwann cells (also known as Terminal schwann cells or Teloglia) are Neuroglia found at the Neuromuscular junction (NMJ) with known functions in synaptic transmission, synaptogenesis, and nerve regeneration. These cells share a common ancestor with both Myelinating and Non-Myelinating Schwann Cells called Neural Crest cells. Perisynaptic Schwann Cells (PSCs) contribute to the tripartite synapse organization in combination with the pre-synaptic nerve and the post-synaptic muscle fiber. PSCs are considered to be the glial component of the Neuromuscular Junction (NMJ) and have a similar functionality to that of Astrocytes in the Central Nervous System. The characteristics of PSCs are based on both external synaptic properties and internal glial properties, where the internal characteristics of PSCs develop based on the associated synapse, for example: the PSCs of a fast-twitch muscle fiber differ from the PSCs of a slow-twitch muscle fiber even when removed from their natural synaptic environment. PSCs of fast-twitch muscle fibers have higher Calcium levels in response to synapse innervation when compared to slow-twitch PSCs. This balance between external and internal influences creates a range of PSCs that are present in the many Neuromuscular Junctions of the Peripheral Nervous System. Perisynaptic schwann cells (also known as Terminal schwann cells or Teloglia) are Neuroglia found at the Neuromuscular junction (NMJ) with known functions in synaptic transmission, synaptogenesis, and nerve regeneration. These cells share a common ancestor with both Myelinating and Non-Myelinating Schwann Cells called Neural Crest cells. Perisynaptic Schwann Cells (PSCs) contribute to the tripartite synapse organization in combination with the pre-synaptic nerve and the post-synaptic muscle fiber. PSCs are considered to be the glial component of the Neuromuscular Junction (NMJ) and have a similar functionality to that of Astrocytes in the Central Nervous System. The characteristics of PSCs are based on both external synaptic properties and internal glial properties, where the internal characteristics of PSCs develop based on the associated synapse, for example: the PSCs of a fast-twitch muscle fiber differ from the PSCs of a slow-twitch muscle fiber even when removed from their natural synaptic environment. PSCs of fast-twitch muscle fibers have higher Calcium levels in response to synapse innervation when compared to slow-twitch PSCs. This balance between external and internal influences creates a range of PSCs that are present in the many Neuromuscular Junctions of the Peripheral Nervous System. Perisynaptic (Terminal) Schwann Cells were first discovered by Louis-Antoine Ranvier in 1878 when he observed branching networks surrounding the motor end plate (neural portion of NMJ). He described PSCs as 'arborisation nuclei' due to their many projections into the synapse seen under the microscope. These cells were distinguished from muscle fibre nuclei and the motor end plate, making the third component of the tripartite synaptic model. It was found that these newly discovered cells were present in nerve degeneration models, showing their non-neural nature. The proximity of PSCs to the motor end plate raised questions about their functionality, but little was known up until the vast research conducted in the past two decades. The origin of Perisynaptic (Terminal) Schwann Cells was largely under question in the 1960s as there were arguments on whether the cells were of epithelial or glial descent, but the development of PSCs has been linked to Neural crest origin. As described above, PSCs are a type of non-myelinating Schwann cell, which develop from neural crest cells. The general series of developmental events can be summarized as this: Neural Crest cells develop into Schwann cell precursors which further develop into Immature Schwann cells which then differentiate into Myelinating Schwann cells and non-Myelinating schwann cells of which Perisynaptic Schwann cells are a subset. Neural crest cells are found in the dorsal neural tube from which nerves and glia alike grow and Neural crest cells are the precursors to many various tissue types including enteric neurons and glia. Schwann cell precursors (a first derivative of Neural crest cells) are present as the nerve axon grows from the dorsal neural tube, but it has been shown that these glial precursors are not essential to axonal growth. The transition from neural crest cells to Schwann cell precursors is characterized by Sox10 and generally occurs around embryonic day 12-13 in rats. Schwann cell precursors then differentiate into Immature Schwann cells from which myelinating and non-myelinating Schwann cells are directly descended. These cells generally appear around embryonic day 13-15 in rats. The differentation of Immature Schwann cells occurs after birth and is dependent on the axons in which the glia are associated. This differentation is known to be reversible, as seen in regeneration models. Perisynaptic Schwann cells develop as non-myelinating Schwann cells and encapsulate the NMJ. PSCs can be attributed to glial lineage by the presence of Calcium binding proteins S100, Glial fibrillary acidic protein (GFAP), and Protein 0. These proteins are seen in other glial cells such as Myelinating Schwann cells and Neural Crest cells. While the lineage of non-Myelinating Schwann cells is known from neural crest cells, the exact development of PSCs from non-Myelinating Schwann cells is not fully understood. Synaptogenesis is the formation of a synapse and in this case the Neuromuscular Junction is of interest. In this section, the focus is on the development of the NMJ from the outgrowth of axons during development. As mentioned in the development section, Schwann cell precursors accompany growing axons as they reach their associated muscles. It is now known that these PSC precursors are not essential to axonal growth, but when present they guide growth cones and help with the maintenance of NMJs after they are formed. After the initial nervous-muscle interface is formed, there is a striking growth in the number of PSCs at each newly developed NMJ. If, however, there is a lack of PSCs (for example in an ablated model) once the NMJ is formed, there is a lack of further axonal growth or even a retraction of axons can be observed. This is seen in a study on frog NMJs 8 and 12 days after ablation where there was a 44% retraction rate by the 12th day with no PSCs. This retraction shows that PSCs are not essential for the growth of axons, but are essential for the long-term maintenance of NMJs. Cultures have been developed that simulate the functions of PSCs using various cell-derived factors in vitro. These cultures are used to understand the molecular basis for which PSCs promote synaptogenesis. From these cultures it has been found that TGF-ß1 (transforming growth factor-ß1) is essential for the development of synapses in vitro. This TGF-ß1 appears to stop nerve growth in order to promote the nerve-muscle synapse formation, however its role in vivo is unknown. It is known that PSCs are essential for the maintenance of NMJs during development, but PSCs are essential for mature NMJ as well. In frog ablation models, there is observable difference in NMJ properties that arise approximately seven days after PSCs were selectively removed. These changes include both structural and functional abnormalities. In ablation models, samples were taken at regular intervals following removal of PSCs. Immediately following ablatio (at 5 hours), there were no noticeable differences in synaptic structure or functionality. Motor-end plate potentials were unaltered in the pre-ablated and the 5 hour ablated models, showing that PSCs are not essential for short-term maintenance of the NMJ. Approximately 13% of ablated NMJ were observed to be retracted partially or entirely one week after ablation and there was a 50% decrease in end plate potential frequency, meaning the NMJs were firing approximately half as often! This same ablation model cannot be performed in mammals, as the antibody mAB sA12 used in the frog model does not ablate mammalian PSCs. The mammalian PSC, when treated with antibodies against gangliosides in Miller-Fisher Syndrome, show not change in NMJ properties in the short-term, but long-term data has not collected. It can be gathered that PSCs play an important role in long-term maintenance of frog NMJ, but it is unknown if the same effects are true in mammalian NMJs.