Mutations of brainstem transcription factors and central respiratory disorders

Blanchi, Bruno; Sieweke, Michael H.

doi:10.1016/j.molmed.2004.11.005

Cited by 37 publications

(22 citation statements)

References 71 publications

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“…Phox2b-expressing cells are distributed in several regions of the hindbrain involved in the autonomic nervous system in embryonic, neonatal, and adult rodents (Dauger et al, 2003;Kang et al, 2007). Heterozygous mutations of PHOX2B in the form of polyalanine expansions or frameshifts cause congenital central hypoventilation syndrome (CCHS) and late-onset CHS (LO-CHS), symptoms of which manifest in adulthood (Amiel et al, 2003;Blanchi and Sieweke, 2005;Weese-Mayer et al, 2005). Mice bearing mutations with polyalanine expansion (Phox2b 27Ala/ϩ ) lack Phox2b-expressing glutamatergic neurons in the parafacial region of the ventral medulla (Dubreuil et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

CO₂-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

Onimaru¹,

Ikeda²,

Kawakami³

2008

J. Neurosci.

145

161

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Phox2b protein is a specific marker for neurons in the parafacial region of the ventral medulla, which are proposed to play a role in central chemoreception and postnatal survival. Mutations of PHOX2B cause congenital central hypoventilation syndrome. However, there have been no reports concerning electrophysiological characteristics of these Phox2b-expressing neurons in the parafacial region of the neonate immediately after birth. This region overlaps with the parafacial respiratory group (pFRG) composed predominantly of preinspiratory (Pre-I) neurons that are involved in respiratory rhythm generation. We studied (1) whether pFRG neurons are Phox2b immunoreactive or not and (2) whether they show intrinsic CO 2 chemosensitivity. We found that most pFRG/Pre-I neurons were Phox2b immunoreactive and depolarized upon increase in CO 2 concentration under condition of action potential-dependent synaptic transmission blockade by tetrodotoxin. We also confirmed that these pFRG neurons expressed neurokinin-1 receptor. They were tyrosine hydroxylase negative and presumed to be glutamatergic. Our findings suggest that Phox2b-expressing parafacial neurons play a role in respiratory rhythm generation as well as central chemoreception and thus are essential for postnatal survival.

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Section: Introductionmentioning

confidence: 99%

CO₂-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

Onimaru¹,

Ikeda²,

Kawakami³

2008

J. Neurosci.

145

161

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“…To further analyze the requirement for MafB in this process, we generated MafB-deficient mice. Since these mice die at birth from defects of respiratory neurons in the hindbrain and subsequent central breathing failure (4,5), we analyzed macrophage development by in vitro differentiation and in the embryo and in adult mice reconstituted with MafBdeficient fetal liver cells. Surprisingly, we observed normal numbers of Mac-1 ϩ /F4/80 ϩ monocytes and macrophages in all analyzed tissues.…”

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confidence: 99%

Development of Macrophages with Altered Actin Organization in the Absence of MafB

Aziz

Vanhille

Mohideen

et al. 2006

Molecular and Cellular Biology

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In the hematopoietic system the bZip transcription factor MafB is selectively expressed at high levels in monocytes and macrophages and promotes macrophage differentiation in myeloid progenitors, whereas a dominant-negative allele can inhibit this process. To analyze the requirement of MafB for macrophage development, we generated MafB-deficient mice and, due to their neonatal lethal phenotype, analyzed macrophage differentiation in vitro, in the embryo, and in reconstituted mice. Surprisingly we observed in vitro differentiation of macrophages from E14.5 fetal liver (FL) cells and E18.5 splenocytes. Furthermore we found normal numbers of F4/80 ؉ /Mac-1 ؉ macrophages and monocytes in fetal liver, spleen, and blood as well as in bone marrow, spleen, and peritoneum of adult MafB ؊/؊ FL reconstituted mice. MafB ؊/؊ macrophages showed intact basic macrophage functions such as phagocytosis of latex beads or Listeria monocytogenes and nitric oxide production in response to lipopolysaccharide. By contrast, MafB ؊/؊ macrophages expressed increased levels of multiple genes involved in actin organization. Consistent with this, phalloidin staining revealed an altered morphology involving increased numbers of branched protrusions of MafB ؊/؊ macrophages in response to macrophage colony-stimulating factor. Together these data point to an unexpected redundancy of MafB function in macrophage differentiation and a previously unknown role in actin-dependent macrophage morphology.

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“…An inappropriate response in strength can contribute to respiratory control instability and may result in the occurrence of an apnoeic event. Likewise, a response that is too fast or too slow can destabilize the blood gas level and can contribute to the onset of bouts of periodic breathing [3,10]. From the present study, it is suggested that PTT has moderate Se and Sp to identify central SAH events from normal breathing.…”

Section: Discussionmentioning

confidence: 70%

“…The clinical symptoms and PSG characteristics of SAH for infants differ from those in children and adults [1,2]. Infantile SAH usually results from congenital facial anomalies and neurological abnormalities that involve muscle tone and upper airway control [2,3]. Unlike children and adults, SAH in an infant can present a unique threat to life, such as sudden infant death syndrome and premature apnoea.…”

Section: Introductionmentioning

confidence: 99%

An investigation on pulse transit time in respiratory sleep studies for infants

Foo

Lim

2008

Journal of Medical Engineering & Technology

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The main objective of this study was to assess the capability of pulse transit time (PTT) to identify obstructive and/or central apnoeas from normal breathing patterns in sleeping infants. Clinical trials were conducted with PTT being monitored as an adjunct measure in routine overnight polysomnography (PSG) studies. Standard PSG scorings of events were performed by two blinded observers to evaluate PTT accuracy. Data from eight infants (six male; aged 8.5 + 2.1 months; apnoea-hypopnoea index of 12.1 + 8.4 events per hour) were collected. Obstructive events were not successfully identified by PTT due to their low occurrence. However, PTT scored positive and negative predictive values of 0.803 and 0.788 for central events, respectively. Preliminary findings suggest that PTT has the potential to differentiate normal breathing from central events only in sleeping infants.

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Mutations of brainstem transcription factors and central respiratory disorders

Cited by 37 publications

References 71 publications

CO₂-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

CO₂-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

Development of Macrophages with Altered Actin Organization in the Absence of MafB

An investigation on pulse transit time in respiratory sleep studies for infants

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Mutations of brainstem transcription factors and central respiratory disorders

Cited by 37 publications

References 71 publications

CO2-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

CO2-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

Development of Macrophages with Altered Actin Organization in the Absence of MafB

An investigation on pulse transit time in respiratory sleep studies for infants

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CO₂-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat

CO₂-Sensitive Preinspiratory Neurons of the Parafacial Respiratory Group Express Phox2b in the Neonatal Rat