Respiratory physiology & neurobiology
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Phox2b-expressing cells in the parafacial region of the ventral medulla are proposed to play a role in central chemoreception and postnatal survival. Recent findings in the adult rat and neonatal mouse suggest that the Phox2b-immunoreactive (ir) cell cluster in the rostral ventrolateral medulla is composed of glutamatergic neurons and expresses neurokinin 1 receptor (NK1R), indicating that the cluster may be identical to the retrotrapezoid nucleus. ⋯ Our findings suggest that Phox2b-expressing pFRG/Pre-I neurons play a role in respiratory rhythm generation as well as central chemoreception and thus are essential for postnatal survival. In this brief review, we focused on these recent findings and discuss the functional role of pFRG/Pre-I neurons.
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Respir Physiol Neurobiol · Aug 2009
Ampakine therapy to counter fentanyl-induced respiratory depression.
Opioid analgesics are the most widely used and effective pharmacological agents for the treatment of acute, postoperative and chronic pain. However, activation of opiate receptors leads to significant depression of respiratory frequency in a subpopulation of patients. Here we test the hypothesis that the AMPAKINE CX717 is effective for alleviating fentanyl-induced respiratory depression without interfering with analgesia. ⋯ AMPA receptor mediated conductances play a central role in controlling respiratory rhythmogenesis and drive to motoneurons. Here, we demonstrate that CX717 counters fentanyl-induced respiratory depression without significantly altering analgesia and sedation, or noticeably affecting the animals' behavior. Collectively, the preclinical data demonstrate the significant potential for the use of ampakines in respiratory medicine.
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Respir Physiol Neurobiol · Aug 2009
PHOX2B in respiratory control: lessons from congenital central hypoventilation syndrome and its mouse models.
Phox2b is a master regulator of visceral reflex circuits. Its role in the control of respiration has been highlighted by the identification of heterozygous PHOX2B mutations as the cause of Central Congenital Hypoventilation Syndrome (CCHS), a rare disease defined by the lack of CO(2) responsiveness and of breathing automaticity in sleep. Phox2b(27Ala/+) mice that bear a frequent CCHS-causing mutation do not respond to hypercapnia and die in the first hour after birth from central apnoea. ⋯ Neurons of the retrotrapezoïd nucleus/parafacial respiratory group (RTN/pFRG) were found severely depleted in these mice and no other neuronal loss could be identified. Physiological experiments show that RTN/pFRG neurons are crucial to driving proper breathing at birth and are necessary for central chemoreception and the generation of a normal respiratory rhythm. To date, the reason for the selective vulnerability of RTN/pFRG neurons to PHOX2B protein dysfunction remains unexplained.