Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss
Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2021.658990/full |
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| author | Jérôme Ruel Jérôme Ruel Matthieu J. Guitton Paul Gratias Marc Lenoir Sanbing Shen Jean-Luc Puel Philippe Brabet Jing Wang |
| author_facet | Jérôme Ruel Jérôme Ruel Matthieu J. Guitton Paul Gratias Marc Lenoir Sanbing Shen Jean-Luc Puel Philippe Brabet Jing Wang |
| author_sort | Jérôme Ruel |
| collection | DOAJ |
| description | Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout the body, PACAP functions as neuromodulators and neuroprotectors, rescuing neurons from apoptosis, mostly through the PAC1 receptor. To explore the potential protective effect of endogenous PACAP against Noise-induced hearing loss (NIHL), we used a knockout mouse model lacking PAC1 receptor expression (PACR1−/−) and a transgenic humanized mouse model expressing the human PAC1 receptor (TgHPAC1R). Based on complementary approaches combining electrophysiological, histochemical, and molecular biological evaluations, we show PAC1R expression in spiral ganglion neurons and in cochlear apical cells of the organ of Corti. Wild-type (WT), PAC1R−/−, and TgHPAC1R mice exhibit similar auditory thresholds. For most of the frequencies tested after acute noise damage, however, PAC1R−/− mice showed a larger elevation of the auditory threshold than did their WT counterparts. By contrast, in a transgene copy number-dependent fashion, TgHPAC1R mice showed smaller noise-induced elevations of auditory thresholds compared to their WT counterparts. Together, these findings suggest that PACAP could be a candidate for endogenous protection against noise-induced hearing loss. |
| first_indexed | 2024-12-22T17:47:31Z |
| format | Article |
| id | doaj.art-fb1c3c219f4446ea9e62abbc1c4503dc |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T17:47:31Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-fb1c3c219f4446ea9e62abbc1c4503dc2022-12-21T18:18:15ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022021-03-011510.3389/fncel.2021.658990658990Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing LossJérôme Ruel0Jérôme Ruel1Matthieu J. Guitton2Paul Gratias3Marc Lenoir4Sanbing Shen5Jean-Luc Puel6Philippe Brabet7Jing Wang8Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, FranceLaboratoire de Neurosciences Cognitives, UMR7291 CNRS, Aix-Marseille Université, Marseille, FranceCERVO Brain Research Center, Faculty of Medicine, Laval University, Quebec City, QC, CanadaInstitute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, FranceInstitute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, FranceRegenerative Medicine Institute, National University of Ireland (NUI), Galway, IrelandInstitute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, FranceInstitute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, FranceInstitute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, FrancePituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout the body, PACAP functions as neuromodulators and neuroprotectors, rescuing neurons from apoptosis, mostly through the PAC1 receptor. To explore the potential protective effect of endogenous PACAP against Noise-induced hearing loss (NIHL), we used a knockout mouse model lacking PAC1 receptor expression (PACR1−/−) and a transgenic humanized mouse model expressing the human PAC1 receptor (TgHPAC1R). Based on complementary approaches combining electrophysiological, histochemical, and molecular biological evaluations, we show PAC1R expression in spiral ganglion neurons and in cochlear apical cells of the organ of Corti. Wild-type (WT), PAC1R−/−, and TgHPAC1R mice exhibit similar auditory thresholds. For most of the frequencies tested after acute noise damage, however, PAC1R−/− mice showed a larger elevation of the auditory threshold than did their WT counterparts. By contrast, in a transgene copy number-dependent fashion, TgHPAC1R mice showed smaller noise-induced elevations of auditory thresholds compared to their WT counterparts. Together, these findings suggest that PACAP could be a candidate for endogenous protection against noise-induced hearing loss.https://www.frontiersin.org/articles/10.3389/fncel.2021.658990/fullacoustic traumaPACAP (pituitary adenylate cyclase-activating polypeptide)PAC1 receptorneuroprotectionnoise-induced hearing loss (NIHL) |
| spellingShingle | Jérôme Ruel Jérôme Ruel Matthieu J. Guitton Paul Gratias Marc Lenoir Sanbing Shen Jean-Luc Puel Philippe Brabet Jing Wang Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss Frontiers in Cellular Neuroscience acoustic trauma PACAP (pituitary adenylate cyclase-activating polypeptide) PAC1 receptor neuroprotection noise-induced hearing loss (NIHL) |
| title | Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss |
| title_full | Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss |
| title_fullStr | Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss |
| title_full_unstemmed | Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss |
| title_short | Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss |
| title_sort | endogenous pituitary adenylate cyclase activating polypeptide pacap plays a protective effect against noise induced hearing loss |
| topic | acoustic trauma PACAP (pituitary adenylate cyclase-activating polypeptide) PAC1 receptor neuroprotection noise-induced hearing loss (NIHL) |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2021.658990/full |
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