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Disease
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Target Concepts:
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Query: UMLS:C0037315 (
sleep apnea
)
8,000
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Central congenital hypoventilation syndrome is caused by mutations of the gene that encodes the transcription factor Phox2b. The syndrome is characterized by a severe form of
sleep apnea
attributed to greatly compromised central and peripheral chemoreflexes. In this study, we analyze whether Phox2b expression in the brainstem respiratory network is preferentially associated with neurons involved in chemosensory integration in rats. At the very rostral end of the ventral respiratory column (VRC), Phox2b was present in many VGlut2 (
vesicular glutamate transporter 2
) mRNA-containing neurons. These neurons were functionally identified as the respiratory chemoreceptors of the retrotrapezoid nucleus (RTN). More caudally in the VRC, many fewer neurons expressed Phox2b. These cells were not part of the central respiratory pattern generator (CPG), because they were typically cholinergic visceral motor neurons or catecholaminergic neurons (presumed C1 neurons). Phox2b was not detected in serotonergic neurons, in the A5, A6, and A7 noradrenergic cell groups nor within the main cardiorespiratory centers of the dorsolateral pons. Phox2b was expressed by many solitary tract nucleus (NTS) neurons including those that relay peripheral chemoreceptor information to the RTN. These and previous observations by others suggest that Phox2b is expressed by an uninterrupted chain of neurons involved in the integration of peripheral and central chemoreception (carotid bodies, chemoreceptor afferents, chemoresponsive NTS neurons projecting to VRC, RTN chemoreceptors). The presence of Phox2b in this circuit and its apparent absence from the respiratory CPG could explain why Phox2b mutations disrupt breathing automaticity during sleep without causing major impairment of respiration during waking.
...
PMID:Expression of Phox2b by brainstem neurons involved in chemosensory integration in the adult rat. 1702 Nov 86
We wanted to understand the brain circuitry that awakens the individual when there is elevated CO
2
or low O
2
(e.g., during
sleep apnea
or asphyxia). The sensory signals for high CO
2
and low O
2
all converge on the parabrachial nucleus (PB) of the pons, which contains neurons that project to the forebrain. So, we first deleted the
vesicular glutamate transporter 2
, necessary to load glutamate into synaptic vesicles, from neurons in the PB, and showed that this prevents awakening to high CO
2
or low O
2
We then showed that PB neurons that express calcitonin gene-related peptide (CGRP) show cFos staining during high CO
2
Using CGRP-Cre-ER mice, we expressed the inhibitory opsin archaerhodopsin just in the PB
CGRP
neurons. Photoinhibition of the PB
CGRP
neurons effectively prevented awakening to high CO
2
, as did photoinhibition of their terminals in the basal forebrain, amygdala, and lateral hypothalamus. The PB
CGRP
neurons are a key mediator of the wakening response to apnea.
...
PMID:Brain Circuitry for Arousal from Apnea. 3101 81
