Atrial Natriuretic Peptide Improves Neurite Outgrowth from Spiral Ganglion Neurons In Vitro through a cGMP-Dependent Manner

Abstract

The spiral ganglion neurons (SGNs) are the primary afferent neurons in the spiral ganglion (SG), while their degeneration or loss would cause sensorineural hearing loss. As a cardiac-derived hormone, atrial natriuretic peptide (ANP) plays a critical role in cardiovascular homeostasis through binding to its functional receptors (NPR-A and NPR-C). ANP and its receptors are widely expressed in the mammalian nervous system where they could be implicated in the regulation of multiple neural functions. Although previous studies have provided direct evidence for the presence of ANP and its functional receptors in the inner ear, their presence within the cochlear SG and their regulatory roles during auditory neurotransmission and development remain largely unknown. Based on our previous findings, we investigated the expression patterns of ANP and its receptors in the cochlear SG and dissociated SGNs and determined the influence of ANP on neurite outgrowth in vitro by using organotypic SG explants and dissociated SGN cultures from postnatal rats. We have demonstrated that ANP and its receptors are expressed in neurons within the cochlear SG of postnatal rat, while ANP may promote neurite outgrowth of SGNs via the NPR-A/cGMP/PKG pathway in a dose-dependent manner. These results indicate that ANP would play a role in normal neuritogenesis of SGN during cochlear development and represents a potential therapeutic candidate to enhance regeneration and regrowth of SGN neurites.

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

“…As shown in Figure 2 , ANP ( Figure 2A ) and its receptors’ ( Figures 2B,C ) immunoreactivities were observed in the SG regions along the length of the cochlear tonotopic axis without any noticeable apical-to-basal gradients. The representative images of cryosectioned tissues from the mid-cochlear turn revealed that the immunoreactivities of ANP ( Figure 2A 2 ), NPR-A ( Figure 2B 2 ), or NPR-C ( Figure 2C 2 ) were colocalized with TUJ1-positive neuronal somata of SGNs, which was consistent with our previous results ( Sun et al, 2013 , 2014 , 2020 ). The similar distribution patterns of ANP ( Figure 2A 2’ ), NPR-A ( Figure 2B 2’ ), and NPR-C ( Figure 2C 2’ ) were observed in the cochlear SGNs, and they were predominantly immunoreactive in the neuronal perikarya, including the cytoplasm and plasma membrane of SGNs.…”

“…Sci. Rep. 6:29621. doi: 10.1038/srep29621 He, Z.-H., Zou, S.-Y., Li, M., Liao, F.-L., Wu, X., Sun, H.-Y., et al (2020). The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.…”

“…The existence of ANP and receptors in the sensory and secretory compartments of the mammalian inner ear has been systematically elucidated in a great number of literatures ( Lamprecht and Meyer zum Gottesberge, 1988 ; Meyer and Lamprecht, 1989 ; Gottesberge et al, 1991 ; Koch et al, 1992 ; Yoon and Hellström, 1992 ; Yoon and Anniko, 1994 ; Furuta et al, 1995 ; Meyer Zum Gottesberge et al, 1995 ; Krause et al, 1997 ; Suzuki et al, 1998 ; Seebacher et al, 1999 ; Yoon et al, 2012 ; Sun et al, 2013 , 2014 ; Yoon et al, 2015 ; Sun et al, 2020 ), while recent works also show that ANP receptors are distributed in rat cochlear SG and modiolus of the guinea pig ( Lamprecht and Meyer zum Gottesberge, 1988 ; Furuta et al, 1995 ). However, the distribution patterns and potential functions of ANP and its receptors in the neural elements of the inner ear remain unclear.…”

“…In our previous studies, the expression patterns of ANP and its receptors were investigated in the cochlear SG, which provided direct evidence for the presence and synthesis of ANP and its receptors in the neural region of the cochlea ( Sun et al, 2013 , 2014 ). We recently demonstrated that ANP might promote neurite outgrowth of cochlear SGNs by triggering the NPR-A/cGMP/PKG pathway in a dose-dependent manner ( Sun et al, 2020 ). In the current study, the influence of ANP on neurite outgrowth, neurite attraction, and neuronal survival of rat SGNs was evaluated by employing organotypic explant and dissociated neuron cultures in vitro .…”

1800 MHz Radiofrequency Electromagnetic Field Impairs Neurite Outgrowth Through Inhibiting EPHA5 Signaling

“…These pathways were directly related to neurite development. Also, the enriched items included some pathways which have been demonstrated closely related to neurite development, such as the PI3K-AKT signaling pathway (Zhao et al, 2020), mTOR signaling pathway (Wen et al, 2020), cGMP-PKG signaling pathway (Sun et al, 2020), thyroid hormone signaling pathway (Poddar et al, 1996), and calcium signaling pathway (Zhao et al, 2019; Figure 2E).…”