| First Author | Vogelgesang S | Year | 2018 |
| Journal | Front Mol Neurosci | Volume | 11 |
| Pages | 28 | PubMed ID | 29515365 |
| Mgi Jnum | J:289512 | Mgi Id | MGI:6433662 |
| Doi | 10.3389/fnmol.2018.00028 | Citation | Vogelgesang S, et al. (2018) Persistent Expression of Serotonin Receptor 5b Alters Breathing Behavior in Male MeCP2 Knockout Mice. Front Mol Neurosci 11:28 |
| abstractText | Mutations in the transcription factor methyl-CpG-binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome (RTT). Besides many other neurological problems, RTT patients show irregular breathing with recurrent apneas or breath-holdings. MeCP2-deficient mice, which recapitulate this breathing phenotype, show a dysregulated, persistent expression of G-protein-coupled serotonin receptor 5-ht5b (Htr5b) in the brainstem. To investigate whether the persistence of 5-ht5b expression is contributing to the respiratory phenotype, we crossbred MeCP2-deficient mice with 5-ht5b-deficient mice to generate double knockout mice (Mecp2(-/y) ;Htr5b(-/-)). To compare respiration between wild type (WT), Mecp2(-/y) and Mecp2(-/y) ;Htr5b(-/-) mice, we used unrestrained whole-body plethysmography. While the breathing of MeCP2-deficient male mice (Mecp2(-/y) ) at postnatal day 40 is characterized by a slow breathing rate and the occurrence of prolonged respiratory pauses, we found that in MeCP2-deficient mice, which also lacked the 5-ht5b receptor, the breathing rate and the number of pauses were indistinguishable from WT mice. To test for a potential mechanism, we also analyzed if the known coupling of 5-ht5b receptors to Gi proteins is altering second messenger signaling. Tissue cAMP levels in the medulla of Mecp2(-/y) mice were decreased as compared to WT mice. In contrast, cAMP levels in Mecp2(-/y) ;Htr5b(-/-) mice were indistinguishable from WT mice. Taken together, our data points towards a role of 5-ht5b receptors within the complex breathing phenotype of MeCP2-deficient mice. |
