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LRP1 FUNCTIONS AS A NEUROTROPHIC RECEPTOR IN DORSAL ROOT GANGLION SENSORY NEURONS: GP39.

Yamauchi, Kazuyo1; Mantuano, Elisabetta2; Yamauchi, Tomonori3; Takahashi, Kazuhisa4; Gonias, Steven L.5; Campana, Marie W.2

Spine Journal Meeting Abstracts: October 2011 - Volume - Issue - [no page #]
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1UCSD and Chiba University, Anesthesiology and Orthopaedic Surgery, La Jolla, US;

2UCSD, Anesthesiology, La Jolla, US; 3UCSD and Chiba University, Anesthesiology and Pathology and Orthopaedic surgery, La Jolla, US;4Chiba University, Orthopaedic Surgery, Chiba, Japan; 5UCSD, Pathology, La Jolla, CA, US

INTRODUCTION: The pathological mechanism of discogenic low back pain is supposed to be sensory nerve ingrowth into the inner layers of the discs. The effect of neurotrophic receptor is considered to be important for mediating nerve growth. LRP1 also is expressed by many neuronal populations and has been implicated in nerve growth by a pathway that may involve Src family kinases (SFK). The goal of this study was to determine whether LRP1 functions as a neurotrophic receptor in sensory neurons.

METHODS: Primary cultures of DRG were prepared from rat embryos (day 15). The LRP1‐binding domain of α2‐macroglobulin (RBD) or GST as negative control or NGF as positive control was treated immediately after plating DRG. And, it was performed whether RBD was related to sensory neuron extension via Src‐mediated pathway using PP2 as Src family kinase inhibiter. DRG were pretreated with or without PP2 for 30min before treatment with RBD or GST or NGF. The ability of each group to promote nerve growth was confirmed by measuring GAP43 mRNA. Furthermore, it was performed immunocytochemistry to investigate for DRG survivability using anti cleaved‐caspase3.

RESULTS: qPCR of GAP43 mRNA after treatment with RBD or NGF were significantly more than one with GST, *p < 0.05. In a word, we considered that RBD induced in nerve growth comparable to NGF. qPCR of GAP43 mRNA after treatment with RBD or NGF or NGF+PP2 were significantly more than one with GST, *p < 0.05. RBD+PP2 was not significantly compared with GST. Therefore, PP2 blocked nerve growth in response to the RBD but not NGF. As the result of immunocytochemistry, cleavedcaspase3 positive cells which were treated with RBD or NGF less than treated one with GST. It suggested that RBD enhanced cell survivability.

DISCUSSION: These results suggest that LRP1 ligands in sensory neurons activate the SFK dependent pathway. The ability of LRP1 in sensory neurons to promote survival, nerve growth qualifies LRP1 as a true neurotrophic receptor.

© 2011 Lippincott Williams & Wilkins, Inc.