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Unexpected association of the "inhibitory" neuroligin 2 with excitatory PSD95 in neuropathic pain.

Authors: Dolique, T  Favereaux, A  Roca-Lapirot, O  Roques, V  Leger, C  Landry, M  Nagy, F 
Citation: Dolique T, etal., Pain. 2013 Nov;154(11):2529-46. doi: 10.1016/j.pain.2013.07.035. Epub 2013 Jul 25.
Pubmed: (View Article at PubMed) PMID:23891900
DOI: Full-text: DOI:10.1016/j.pain.2013.07.035

In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the spinal dorsal horn. We investigated the deregulation of the synaptogenic neuroligin (NL) molecules, whose NL1 and NL2 isoforms are primarily encountered at excitatory and inhibitory synapses, respectively. In the dorsal horn of SNL rats, NL2 was overexpressed whereas NL1 remained unchanged. In control animals, intrathecal injections of small interfering RNA (siRNA) targeting NL2 increased mechanical sensitivity, which confirmed the association of NL2 with inhibition. By contrast, siRNA application produced antinociceptive effects in SNL rats. Regarding NL partners, expression of the excitatory postsynaptic scaffolding protein PSD95 unexpectedly covaried with NL2 overexpression, and NL2/PSD95 protein interaction and colocalization increased. Expression of the inhibitory scaffolding protein gephyrin remained unchanged, indicating a partial change in NL2 postsynaptic partners in SNL rats. This phenomenon appears to be specific to the NL2(-) isoform. Our data showed unexpected upregulation and pronociceptive effects of the "inhibitory" NL2 in neuropathic pain, suggesting a functional shift of NL2 from inhibition to excitation that changed the synaptic ratio toward higher excitation.

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RGD Object Information
RGD ID: 9831150
Created: 2015-02-26
Species: All species
Last Modified: 2015-02-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.