Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling
The complex mechanism by which stress can affect sensory processes such as hearing is still poorly understood. In a previous study, the mineralocorticoid (MR) and/or glucocorticoid receptor (GR) were deleted in frontal brain regions but not cochlear regions using a CaMKIIα-based tamoxifen-inducible...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1017761/full |
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| author | Dila Calis Morgan Hess Philine Marchetta Wibke Singer Julian Modro Ellis Nelissen Jos Prickaerts Peter Sandner Robert Lukowski Peter Ruth Marlies Knipper Lukas Rüttiger |
| author_facet | Dila Calis Morgan Hess Philine Marchetta Wibke Singer Julian Modro Ellis Nelissen Jos Prickaerts Peter Sandner Robert Lukowski Peter Ruth Marlies Knipper Lukas Rüttiger |
| author_sort | Dila Calis |
| collection | DOAJ |
| description | The complex mechanism by which stress can affect sensory processes such as hearing is still poorly understood. In a previous study, the mineralocorticoid (MR) and/or glucocorticoid receptor (GR) were deleted in frontal brain regions but not cochlear regions using a CaMKIIα-based tamoxifen-inducible CreERT2/loxP approach. These mice exhibit either a diminished (MRTMXcKO) or disinhibited (GRTMXcKO) auditory nerve activity. In the present study, we observed that mice differentially were (MRTMXcKO) or were not (GRTMXcKO) able to compensate for altered auditory nerve activity in the central auditory pathway. As previous findings demonstrated a link between central auditory compensation and memory-dependent adaptation processes, we analyzed hippocampal paired-pulse facilitation (PPF) and long-term potentiation (LTP). To determine which molecular mechanisms may impact differences in synaptic plasticity, we analyzed Arc/Arg3.1, known to control AMPA receptor trafficking, as well as regulators of tissue perfusion and energy consumption (NO-GC and GC-A). We observed that the changes in PPF of MRTMXcKOs mirrored the changes in their auditory nerve activity, whereas changes in the LTP of MRTMXcKOs and GRTMXcKOs mirrored instead the changes in their central compensation capacity. Enhanced GR expression levels in MRTMXcKOs suggest that MRs typically suppress GR expression. We observed that hippocampal LTP, GC-A mRNA expression levels, and ABR wave IV/I ratio were all enhanced in animals with elevated GR (MRTMXcKOs) but were all lower or not mobilized in animals with impaired GR expression levels (GRTMXcKOs and MRGRTMXcKOs). This suggests that GC-A may link LTP and auditory neural gain through GR-dependent processes. In addition, enhanced NO-GC expression levels in MR, GR, and MRGRTMXcKOs suggest that both receptors suppress NO-GC; on the other hand, elevated Arc/Arg3.1 levels in MRTMXcKOs and MRGRTMXcKOs but not GRTMXcKOs suggest that MR suppresses Arc/Arg3.1 expression levels. Conclusively, MR through GR inhibition may define the threshold for hemodynamic responses for LTP and auditory neural gain associated with GC-A. |
| first_indexed | 2024-04-10T09:39:15Z |
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| language | English |
| last_indexed | 2024-04-10T09:39:15Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-f7aee9edee2a44ba8bdb50c11b726da72023-02-17T16:05:24ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-02-011610.3389/fnmol.2023.10177611017761Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signalingDila Calis0Morgan Hess1Philine Marchetta2Wibke Singer3Julian Modro4Ellis Nelissen5Jos Prickaerts6Peter Sandner7Robert Lukowski8Peter Ruth9Marlies Knipper10Lukas Rüttiger11Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, GermanyDepartment of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, GermanyDepartment of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, GermanyDepartment of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, GermanyDepartment of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, GermanyDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, NetherlandsDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, NetherlandsBayer Health Care Pharmaceuticals, Global Drug Discovery Pharma Research Centre Wuppertal, Wuppertal, GermanyInstitute of Pharmacy, Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, Tübingen, GermanyInstitute of Pharmacy, Pharmacology, Toxicology and Clinical Pharmacy, University of Tübingen, Tübingen, GermanyDepartment of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, GermanyDepartment of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, University of Tübingen, Tübingen, GermanyThe complex mechanism by which stress can affect sensory processes such as hearing is still poorly understood. In a previous study, the mineralocorticoid (MR) and/or glucocorticoid receptor (GR) were deleted in frontal brain regions but not cochlear regions using a CaMKIIα-based tamoxifen-inducible CreERT2/loxP approach. These mice exhibit either a diminished (MRTMXcKO) or disinhibited (GRTMXcKO) auditory nerve activity. In the present study, we observed that mice differentially were (MRTMXcKO) or were not (GRTMXcKO) able to compensate for altered auditory nerve activity in the central auditory pathway. As previous findings demonstrated a link between central auditory compensation and memory-dependent adaptation processes, we analyzed hippocampal paired-pulse facilitation (PPF) and long-term potentiation (LTP). To determine which molecular mechanisms may impact differences in synaptic plasticity, we analyzed Arc/Arg3.1, known to control AMPA receptor trafficking, as well as regulators of tissue perfusion and energy consumption (NO-GC and GC-A). We observed that the changes in PPF of MRTMXcKOs mirrored the changes in their auditory nerve activity, whereas changes in the LTP of MRTMXcKOs and GRTMXcKOs mirrored instead the changes in their central compensation capacity. Enhanced GR expression levels in MRTMXcKOs suggest that MRs typically suppress GR expression. We observed that hippocampal LTP, GC-A mRNA expression levels, and ABR wave IV/I ratio were all enhanced in animals with elevated GR (MRTMXcKOs) but were all lower or not mobilized in animals with impaired GR expression levels (GRTMXcKOs and MRGRTMXcKOs). This suggests that GC-A may link LTP and auditory neural gain through GR-dependent processes. In addition, enhanced NO-GC expression levels in MR, GR, and MRGRTMXcKOs suggest that both receptors suppress NO-GC; on the other hand, elevated Arc/Arg3.1 levels in MRTMXcKOs and MRGRTMXcKOs but not GRTMXcKOs suggest that MR suppresses Arc/Arg3.1 expression levels. Conclusively, MR through GR inhibition may define the threshold for hemodynamic responses for LTP and auditory neural gain associated with GC-A.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1017761/fullglucocorticoid receptormineralocorticoid receptorNO-GCGC-Acognition |
| spellingShingle | Dila Calis Morgan Hess Philine Marchetta Wibke Singer Julian Modro Ellis Nelissen Jos Prickaerts Peter Sandner Robert Lukowski Peter Ruth Marlies Knipper Lukas Rüttiger Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling Frontiers in Molecular Neuroscience glucocorticoid receptor mineralocorticoid receptor NO-GC GC-A cognition |
| title | Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling |
| title_full | Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling |
| title_fullStr | Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling |
| title_full_unstemmed | Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling |
| title_short | Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling |
| title_sort | acute deletion of the central mr gr steroid receptor correlates with changes in ltp auditory neural gain and gc a cgmp signaling |
| topic | glucocorticoid receptor mineralocorticoid receptor NO-GC GC-A cognition |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1017761/full |
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