Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists

Ana Paula Abdala, John Bissonnette, Adrian Newman-Tancredi

Research output: Contribution to journalSpecial issue (Academic Journal)peer-review

24 Citations (Scopus)
503 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number205
Number of pages8
JournalFrontiers in Physiology
Volume5
DOIs
Publication statusPublished - 30 May 2014

Keywords

  • Rett syndrome
  • 5-HT1A receptor
  • breathing
  • anxiety
  • Motor Activity
  • Serotonin
  • Brain Stem
  • vagal tone

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