{"id":140956,"date":"2021-11-16T14:49:41","date_gmt":"2021-11-16T13:49:41","guid":{"rendered":"https:\/\/www.bordeaux-neurocampus.fr\/?p=140956"},"modified":"2021-11-22T18:12:27","modified_gmt":"2021-11-22T17:12:27","slug":"gabriel-pitollat-and-al-in-ajrccm","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/gabriel-pitollat-and-al-in-ajrccm\/","title":{"rendered":"Gabriel Pitollat and al in AJRCCM<\/em>"},"content":{"rendered":"

Congenital Central Hypoventilation Syndrome (CCHS) is characterized by a loss of ventilatory chemosensitivity and life-threatening hypoventilation. Patients require lifelong mechanical ventilation, at least nocturnally. Central apneas are commonly reported in CCHS patients, whereas obstructive apneas may remain unnoticed due to tracheostomy and positive pressure ventilation. CCHS is caused by mutations in the paired-like homeobox 2B gene (PHOX2B<\/em>), the master gene of the autonomic nervous system. In mice, introduction of the most prevalent mutation observed in human (7-alanine expansion, PHOX2B27Ala\/+<\/sup><\/em>) is associated with the main symptoms of CCHS, and agenesis of the retrotrapezoid nucleus, known to provide a major excitatory drive<\/em> to breathing.<\/p>\n

In this publication in AJRCCM we present our work, performed in collaboration with Dr. Jorge Gallego and Boris Matrot (Inserm U1141, H\u00f4pital Robert Debr\u00e9, Universit\u00e9 de Paris, Paris) providing new insights in breathing disorders associated with CCHS. Combining pneumotachography and laser detection of abdominal movements (Figure 1A, B), to classify apneas, we demonstrate that newborn Phox2b27Ala\/+ <\/sup><\/em>mice display an abnormally high degree not only of central apneas, but also of obstructive and mixed apneas (Figure 1C, D). Furthermore, these mice show dysgenesis (Figure 2) and dysfunction of the hypoglossal nucleus, a non-Phox2b<\/em> expressing structure critical to the maintenance of upper airway patency. These results broaden the spectrum of neuroanatomical and neurofunctional disorders caused by Phox2b<\/em> mutations, and point to the clinical importance of also detecting obstructive events in CCHS patients<\/strong>.<\/p>\n

\"\"<\/a><\/em><\/p>\n

Figure 1<\/em><\/strong>: Different types of apneas are detected in CCHS pups.<\/strong> A-B<\/strong>: <\/em>Experimental set up. C-D<\/strong>: <\/em>Traces of flow and simultaneous abdominal movements during the different types of apneic events: central: no respiratory movement, no air flow; obstructive: respiratory movement, no air flow; mixed: some respiratory movements associated or not with air flow.<\/p>\n

 <\/p>\n

\"\"<\/a><\/em><\/strong><\/p>\n

Figure 2: Abnormal anatomy of the hypoglossal nucleus in CCHS mutants.<\/em><\/strong> A:<\/strong><\/em> Schematic representation of brainstem preparations with the location of the main respiratory neural networks (RTN: retrotrapezo\u00efd nucleus; preB\u00f6tC: preB\u00f6tzinger complex). B:<\/strong> Immunostaining against motoneurons (Islet1,2 positive) at the level of the hypoglossal nucleus in wild-type and CCHS mutant (Phox2b27Ala<\/sup>) preparations showing\u00a0 a reduced hypoglossal nucleus.\u00a0 <\/em><\/p>\n

 <\/p>\n

Reference<\/h3>\n

Obstructive Apneas in a Mouse Model of Congenital Central Hypoventilation Syndrome
\n<\/strong>Am\u00e9lia Madani*,\u00a0Gabriel Pitollat*<\/u><\/strong>,\u00a0El\u00e9onore Sizun,\u00a0Laura Cardoit<\/strong>,<\/u>\u00a0Maud Ringot,\u00a0Thomas Bourgeois,\u00a0N\u00e9lina Ramanantsoa,\u00a0Christophe Delclaux,\u00a0St\u00e9phane Dauger,\u00a0Marie-Pia d’Ortho,\u00a0Muriel Thoby-Brisson<\/strong>,\u00a0Jorge Gallego,\u00a0Boris Matrot.
\nAm J Respir Crit Care Med .<\/strong> 2021
\ndoi: 10.1164\/rccm.202104-0887OC.<\/a><\/p>\n

* First co-authors<\/strong><\/p>\n

First co-author<\/h3>\n

Gabriel Pitollat (PhD student at INCIA<\/u>) is funded with a Cifre grant in association with AtmosR<\/p>\n","protected":false},"excerpt":{"rendered":"

Obstructive Apneas in a Mouse Model of Congenital Central Hypoventilation Syndrome<\/p>\n","protected":false},"author":108,"featured_media":141055,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71],"tags":[],"class_list":["post-140956","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlight-en"],"_links":{"self":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/140956","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/users\/108"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/comments?post=140956"}],"version-history":[{"count":3,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/140956\/revisions"}],"predecessor-version":[{"id":141063,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/140956\/revisions\/141063"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media\/141055"}],"wp:attachment":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media?parent=140956"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/categories?post=140956"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/tags?post=140956"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}