Atrial Natriuretic Peptide Promotes Neurite Outgrowth and Survival of Cochlear Spiral Ganglion Neurons in vitro Through NPR-A/cGMP/PKG Signaling

Abstract

Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3’,5’-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptor by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions. Despite former literatures and our reports indicating the existence of ANP and its receptors within the inner ear, particularly in the spiral ganglion, their potential regulatory mechanisms underlying functional properties of auditory neurons are still incompletely understood. Our recently published investigation revealed that ANP could promote the neurite outgrowth of SGNs by activating NPR-A/cGMP/PKG cascade in a dose-dependent manner. In the present research, the influence of ANP and its receptor-mediated downstream signaling pathways on neurite outgrowth, neurite attraction, and neuronal survival of SGNs in vitro was evaluated by employing cultures of organotypic explant and dissociated neuron from postnatal rats. Our data indicated that ANP could support and attract neurite outgrowth of SGNs and possess a high capacity to improve neuronal survival of SGNs against glutamate-induced excitotoxicity by triggering the NPR-A/cGMP/PKG pathway. The neuroregenerative and neuroprotective effects of ANP/NPRA/cGMP/PKG-dependent signaling on SGNs would represent an attractive therapeutic candidate for hearing impairment.

Hypoxic Preconditioned Neural Stem Cell-Derived Extracellular Vesicles Contain Distinct Protein Cargo from Their Normal Counterparts

“…The possibility of Rpl34 as a novel prognostic biomarker and therapeutic target for ischemic stroke was also reported previously [ 48 , 49 ]. Noteworthily, other overexpressed proteins such as Cnp, Cyfip1, Cask, and Tubb5 that were also shown to be overexpressed in our proteomics result are found to be involved in neuronal regulation, protection, maturation, and development [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ].…”

Morphine Re-Arranges Chromatin Spatial Architecture of Primate Cortical Neurons

“…For cellular components, a membrane-bound pattern was profoundly enriched, such as extracellular exosome ( Figure 4 D). Intriguingly, the top 10 pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed the association of DEGs with long-term potentiation (LTP) (0hsa04720), long-term depression (LTD) (0hsa04730), cGMP–PKG signaling (0hsa04022), and axon guidance (0hsa04360) ( Figure 4 E), which have previously been found to play important roles in synaptic plasticity [30] , [31] .…”

Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

“…For cellular components, a membrane-bound pattern was profoundly enriched, such as extracellular exosome (Figure 4D). Intriguingly, the top 10 pathways from KEGG pathway enrichment revealed the association of DEGs with long-term potentiation (LTP) (0hsa04720), long-term depression (LTD) (0hsa04730), cGMP-PKG signaling (0hsa04022), and axon guidance (0hsa04360) (Figure 4E), which have previously been demonstrated to play important roles in synaptic plasticity [30,31].…”