The expression of the chemorepellent Semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease
Section snippets
Results
Since there are no reliable antibodies available specifically recognizing Sema3A protein, Sema3A expression was examined by in situ hybridization and real time quantitative PCR (RT-qPCR). In situ hybridization and RT-qPCR were performed on gastrocnemic muscles from 1, 4, 7, 14, 21, 28, and 60 day old rats, and on adult gastrocnemic muscles at 4, 7, 14, 21, 36, and 60 days following sciatic nerve crush.
Discussion
Here, we show that TSCs located on NMJs of type IIb/x muscle fibers, but not on type I and type IIa muscle fibers, upregulate the expression of the chemorepellent Sema3A after mechanical denervation and following pharmacological blockage of neurotransmission. In addition, we demonstrate that TSCs positioned at the NMJs of type IIb/x muscle fibers in the G93A-hSOD1 mouse model for ALS selectively up-regulate the chemorepellent Sema3A. In contrast to motor nerve terminals on type I and type IIa
Animals and surgical procedures
All surgical and animal care procedures were carried out according to the local guidelines of the experimental animal care committee. Wistar rats (Harlan CPB-Zeist, Netherlands) were housed in group cages, maintained on a 12 h light/dark cycle with ad libitum access to food and water.
Statistical analysis
For the quantitative polymerase chain reaction every third cryostat section (60 μm) of the complete (i.c. postnatal time course study) or the medial (i.c. sciatic nerve crush study) gastrocnemic muscle was used for total RNA isolation. Three animals were used per time point and RT-qPCR reaction was carried out in duplet. The mRNA levels of the housekeeping gene L37a (this gene was chosen because it was stably expressed in the gastrocnemic muscle, while other housekeeping genes were not) were
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Currently working in the Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92186, USA.