Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists
Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrom...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2014-05-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00205/full |
| _version_ | 1818584325074976768 |
|---|---|
| author | Ana Paula Abdala Adrian eNewman-Tancredi John M Bissonnette |
| author_facet | Ana Paula Abdala Adrian eNewman-Tancredi John M Bissonnette |
| author_sort | Ana Paula Abdala |
| collection | DOAJ |
| description | Rett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT1A) biased agonists. We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects. |
| first_indexed | 2024-12-16T08:19:23Z |
| format | Article |
| id | doaj.art-d01be8f416d646d7ab5bc245961cb60a |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-16T08:19:23Z |
| publishDate | 2014-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-d01be8f416d646d7ab5bc245961cb60a2022-12-21T22:38:10ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2014-05-01510.3389/fphys.2014.0020596079Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonistsAna Paula Abdala0Adrian eNewman-Tancredi1John M Bissonnette2University of BristolNeurolixis Inc.Oregon Health & Science UniversityRett syndrome is a neurological disorder caused by loss of function of methyl-CpG-binding protein 2 (MeCP2). Reduced function of this ubiquitous transcriptional regulator has a devastating effect on the central nervous system. One of the most severe and life-threatening presentations of this syndrome is brainstem dysfunction, which results in autonomic disturbances such as breathing deficits, typified by episodes of breathing cessation intercalated with episodes of hyperventilation or irregular breathing. Defects in numerous neurotransmitter systems have been observed in Rett syndrome both in animal models and patients. Here we dedicate special attention to serotonin due to its role in promoting regular breathing, increasing vagal tone, regulating mood, alleviating Parkinsonian-like symptoms and potential for therapeutic translation. A promising new symptomatic strategy currently focuses on regulation of serotonergic function using highly selective serotonin type 1A (5-HT1A) biased agonists. We address this newly emerging therapy for respiratory brainstem dysfunction and challenges for translation with a holistic perspective of Rett syndrome, considering potential mood and motor effects.http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00205/fullAnxietyMotor ActivityRett SyndromeSerotoninbrainstembreathing |
| spellingShingle | Ana Paula Abdala Adrian eNewman-Tancredi John M Bissonnette Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists Frontiers in Physiology Anxiety Motor Activity Rett Syndrome Serotonin brainstem breathing |
| title | Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists |
| title_full | Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists |
| title_fullStr | Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists |
| title_full_unstemmed | Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists |
| title_short | Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists |
| title_sort | pinpointing brainstem mechanisms responsible for autonomic dysfunction in rett syndrome therapeutic perspectives for 5 ht1a agonists |
| topic | Anxiety Motor Activity Rett Syndrome Serotonin brainstem breathing |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2014.00205/full |
| work_keys_str_mv | AT anapaulaabdala pinpointingbrainstemmechanismsresponsibleforautonomicdysfunctioninrettsyndrometherapeuticperspectivesfor5ht1aagonists AT adrianenewmantancredi pinpointingbrainstemmechanismsresponsibleforautonomicdysfunctioninrettsyndrometherapeuticperspectivesfor5ht1aagonists AT johnmbissonnette pinpointingbrainstemmechanismsresponsibleforautonomicdysfunctioninrettsyndrometherapeuticperspectivesfor5ht1aagonists |