ERRγ is downregulated in injured motor neuron subpopulations following brachial plexus root avulsion

Estrogen-related receptor gamma (ERRgamma) is a member of a small group of orphan nuclear receptor transcription factors that have been implicated in several physiological and pathological processes, including placental development, regulation of metabolic genes or disease. The pattern of expression of ERRgamma, its role in neuronal injury and its co-localization with other transcription factors in the spinal cord of rats with brachial plexus injury has not been determined. The expression profile of ERRgamma and its co-localization with RNA binding protein fox-1 homolog 3 (NeuN) or cyclic AMP-dependent transcription factor 3 (ATF-3) in the motor neurons of rats that underwent brachial plexus root avulsion were assessed using western blot analysis, immunohistochemistry and immunofluorescence. Fluorogold (FG) was used to mark neurons whose axons were severed. ATF-3 was expressed in the nuclei of motor neurons whose axons were severed by root avulsion. On day 3 post-avulsion, FG and ATF-3 were all co-localized in the injured motor neurons. The level of ERRgamma protein in the ipsilateral half of injured spinal cords was significantly decreased compared with that in the contralateral half on days 3, 14 and 28 post-avulsion (all P<0.05). The numbers of ERRgamma-positive motor neurons (ERRgamma(on)) were also notably decreased in the ipsilateral side compared with that in the contralateral side on days 14 and 28 post-avulsion, implying that the expression occurred in alpha motor neurons that were progressively being lost, a phenomenon that was expected post-brachial plexus avulsion. Almost all large and small ERRgamma-positive motor neurons were also NeuN-positive (NeuN(on)). However, a few of these were ERRgamma(on)/NeuN(off) (no NeuN signal). Therefore, these results suggested that ERRgamma is a non-specific marker of gamma motor neurons in rats, and therefore, this specific transcriptional program cannot be used to define functionally distinct motor neuron sub-populations. However, its downregulation on the injured side suggests that it is an important component of the response to injury in motor neurons.