Down-regulation of mRNAs for synaptic adhesion molecules neuroligin-2 and -3 and synCAM1 in spinal motoneurons after axotomy
2007 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 503, no 2, 308-318 p.Article in journal (Refereed) Published
After peripheral axotomy, synapses are eliminated from the somata of spinal motoneurons. Recent evidence indicates that synaptic adhesion molecules play a role in maintenance of synaptic contacts, but so far such molecules have not been investigated in the context of synapse elimination after injury. In vitro, the neuroligins (NLGs) and SynCAM1 drive formation of synapses, and RNAi of NLGs results in decreased synaptic input, indicating an important role for these molecules in synaptic biology. To address potential involvement of NLGs and SynCAMs in postinjury synapse elimination, we investigated the mRNA expression of NLG1, -2, and -3; SynCAM1 and -3; and PSD-95 - an intracellular NLG-binding scaffolding protein - in rat spinal motoneurons in control animals and after sciatic nerve transection (SNT). mRNA signals for NLG2, NLG3, SynCAM1, and SynCAM3, but not NLG1, were seen in uninjured motoneurons. Immunoreactivity for SynCAM was seen in close relation to synaptophysin immunoreactivity on the surface of motoneurons and in close relation to neurofilament immunoreactivity in the sciatic nerve. After axotomy, the signals for NLG2, NLG3, and SynCAM1 mRNAs decreased, whereas the signal for NLG1 mRNA remained undetectable and that for SynCAM3 remained at control levels. The signal for PSD-95 mRNA decreased gradually and reached approximately 50% of control values 2 weeks after axotomy. Thus the retrograde response to axotomy of spinal motoneurons involves a rapid down-regulation of NLG2, NLG3, and SynCAM1 mRNAs and a gradual decrease in PSD-95 mRNA. This indicates that down-regulation of synaptic adhesion molecules plays a role in postinjury synapse elimination.
Place, publisher, year, edition, pages
2007. Vol. 503, no 2, 308-318 p.
Analysis of Variance, Animals, Axotomy, Down-Regulation, Female, Immunoglobulins/genetics/*metabolism, Immunohistochemistry, Membrane Proteins/genetics/*metabolism, Motor Neurons/*metabolism, Nerve Degeneration/metabolism, Nerve Tissue Proteins/genetics/*metabolism, RNA; Messenger/*metabolism, Rats, Spinal Cord/cytology/metabolism, Statistics; Nonparametric, Synapses/*metabolism
Medical and Health Sciences Biological Sciences
IdentifiersURN: urn:nbn:se:uu:diva-14830DOI: 10.1002/cne.21382ISI: 000247422400008PubMedID: 17492651OAI: oai:DiVA.org:uu-14830DiVA: diva2:42601