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1.
J Comp Neurol ; 529(13): 3313-3320, 2021 09.
Article in English | MEDLINE | ID: mdl-34008871

ABSTRACT

The retrotrapezoid nucleus (RTN) is a hub for respiratory chemoregulation in the mammal brainstem that integrates chemosensory information from peripheral sites and central relays. Chemosensitive neurons of the RTN express specific genetic and molecular determinants, which have been used to identify RTN precise location within the brainstem of rodents and nonhuman primates. Based on a comparative approach, we hypothesized that among mammals, neurons exhibiting the same specific molecular and genetic signature would have the same function. The co-expression of preprogalanin (PPGAL) and SLC17A6 (VGluT2) mRNAs with duplex in situ hybridization has been studied in formalin fixed paraffin-embedded postmortem human brainstems. Two specimens were processed and analyzed in line with RTN descriptions in adult rats and macaques. Double-labeled PPGAL+/SLC17A6+ neurons were only identified in the parafacial region of the brainstem. These neurons were found surrounding the nucleus of the facial nerve, located ventrally to the nucleus VII on caudal sections, and slightly more dorsally on rostral sections. The expression of neuromedin B (NMB) mRNA as a single marker of chemosensitive RTN neurons has not been confirmed in humans. The location of the RTN in human adults is provided. This should help to develop investigation tools combining anatomic high-resolution imaging and respiratory functional investigations to explore the pathogenic role of the RTN in congenital or acquired neurodegenerative diseases.


Subject(s)
Brain Stem/metabolism , Brain Stem/pathology , Galanin/biosynthesis , Neurons/metabolism , Neurons/pathology , Vesicular Glutamate Transport Protein 2/biosynthesis , Biomarkers/metabolism , Facial Nucleus/metabolism , Facial Nucleus/pathology , Galanin/genetics , Gene Expression , Humans , Trapezoid Body/metabolism , Trapezoid Body/pathology , Vesicular Glutamate Transport Protein 2/genetics
2.
J Comp Neurol ; 527(17): 2875-2884, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31071232

ABSTRACT

Chemosensitivity is a key mechanism for the regulation of breathing in vertebrates. The retrotrapezoid nucleus is a crucial hub for respiratory chemoreception within the brainstem. It integrates chemosensory information that are both peripheral from the carotid bodies (via the nucleus of the solitary tract) and central through the direct sensing of extracellular protons. To date, the location of a genetically defined RTN has only been ascertained in rodents. We first demonstrated that Phox2b, a key determinant for the development of the visceral nervous system and branchiomotor nuclei in the brainstem including the RTN, had a similar distribution in the brainstem of adult macaques compared to adult rats. Second, based on previous description of a specific molecular signature for the RTN in rats, and on an innovative technique for duplex in situ hybridization, we identified parafacial neurons which coexpressed Phox2b and ppGal mRNAs. They were located ventrally to the nucleus of the facial nerve and extended from the caudal part of the nucleus of the superior olive to the rostral tip of the inferior olive. Using the previously described blockface technique, deformations were corrected to allow the proper alignment and stacking of digitized sections, hence providing for the first time a 3D reconstruction of the macaque brainstem, Phox2b distribution and the primate retrotrapezoid nucleus. This description should help bridging the gap between rodents and humans for the description of key respiratory structures in the brainstem.


Subject(s)
Brain Stem/anatomy & histology , Brain Stem/metabolism , Homeodomain Proteins/metabolism , Macaca fascicularis/anatomy & histology , Macaca fascicularis/metabolism , Neurons/metabolism , Transcription Factors/metabolism , Animals , Female , Imaging, Three-Dimensional , Male , Neurons/cytology , RNA, Messenger/metabolism
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