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bioRxiv · 10.1101/2022.09.27.509698

Pericytes control vascular stability and auditory spiral ganglion neuron survival

Zhang, Y.·Neng, L.·Sharma, K.·Hou, Z.·Johnson, A.·Song, J.·Dabdoub, A.·Shi, X.
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Abstract

The inner ear has a rich population of pericytes, a multi-functional mural cell essential for sensory hair cell heath and normal hearing. However, the mechanics of how pericytes contribute to the homeostasis of the auditory vascular-neuronal complex in the spiral ganglion is not yet known. In this study, using an inducible and conditional pericyte depletion mouse (PdgfrbCreERT2+/-; ROSA26iDTR+/-) model, we demonstrate, for the first time, that pericyte depletion causes loss of vascular volume and spiral ganglion neurons (SGNs) and adversely affects hearing sensitivity. Using an in vitro trans-well co-culture system, we show pericytes markedly promote neurite and vascular branch growth in neonatal SGN explants and adult SGNs. The pericyte-controlled neural growth is strongly mediated by pericyte-released exosomes containing vascular endothelial growth factor-A (VEGF-A). Treatment of neonatal SGN explants or adult SGNs with pericyte-derived exosomes significantly enhances angiogenesis, SGN survival, and neurite growth, all of which were inhibited by a selective blocker of the VEGF receptor 2 (Flk1). Our study demonstrates that pericytes in the adult ear are critical for vascular stability and SGN health. Cross-talk between pericytes and SGNs via exosomes is essential for neuronal and vascular health and normal hearing.

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Zhang, Y., Neng, L., Sharma, K., Hou, Z., Johnson, A., Song, J., Dabdoub, A., Shi, X.. 2022-09-28. Pericytes control vascular stability and auditory spiral ganglion neuron survival. https://doi.org/10.1101/2022.09.27.509698

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