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• W179686039 abstract "INTRODUCTION – Central and peripheral structures, as the medullary nuclei and the carotid body, strictly cohoperate for cardiovascular and respiratory regulation. In the literature, comprehensive and unbiased analyses of morphometric parameters and apoptosis phenomena in infant and adult medullary nuclei are still lacking. Data about local expression of different phosphodiesterase isoforms are also still poor. In the carotid body, many different neurotransmitters/neuromodulators, adhesion molecules and signalling transduction components have been identified but data are still lacking about the presence of some of these, such as adrenomedullin (AM), neurotensin receptors, Neural Cell Adhesion Molecule (NCAM), extracellular signal-regulated kinase (ERK), AKT. The aim of the present work was to give a comprehensive analysis of morphometric parameters and apoptosis phenomena in human medullary nuclei and to analyse the presence of the above components in the carotid body. MATERIALS AND METHODS – Materials consisted of medullae oblongatae sampled at autopsy from 22 adults and 10 infants, and carotid bodies sampled at autopsy from 16 adult subjects and 6 foetuses. A morphometric analysis with the optical disector method was performed to calculate the neuronal densities, nuclear volumes and total neuron numbers of medullary nuclei. Apoptosis was also studied by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) and the mean percentages (± Standard Deviation) of TUNEL-positive neurons were morphometrically analysed. The regional distribution and cellular localization of four isozyme forms of the phosphodiesterase 4 (PDE4A, PDE4B, PDE4C and PDE4D) were also studied in 8 of the above adult subjects by in situ hybridization. In the study of the carotid body, we analysed by immunocytochemistry and double immunofluorescence the expression of AM, neurotensin receptor 1 (NTR1), NCAM, ERK and pERK, AKT and pAKT. AM, ERK/pERK and AKT/pAKT were also studied in foetal samples.RESULTS – In both adults and infants, higher neuronal densities were found in the more ventrally located nuclei of the spinal trigeminal tract (NSTT) (mean values ± Standard Deviation: 9217±2146 n/mm3 and 21347±5006 n/mm3, respectively) and inferior olivary complex (PION: 9149±1341 n/mm3 and 20910±1582 n/mm3; MION: 10102±3024 n/mm3 and 19267±3475 n/mm3; DION: 11318±3704 n/mm3 and 23124±6740 n/mm3, respectively) than in the nuclei of the medullary tegmentum, i.e., hypoglossal nucleus (XII) (1070±343.4 n/mm3 and 2799±1292 n/mm3), dorsal motor nucleus of the vagus (DMNV) (1663±431.4 n/mm3 and 2915±568.1 n/mm3), nucleus tractus solitarii (NTS) (2982±639.9 n/mm3 and 8150±1735 n/mm3), medial vestibular nucleus (MedVe) (2964±380.8 n/mm3 and 6958±1076 n/mm3) and cuneate nucleus (Cu) (1061±238.7 n/mm3 and 2686±843.6 n/mm3). All the medullary nuclei showed higher volumes and lower neuronal densities in adults than in infants, without statistically significant differences in total neuron numbers. Statistically significant differences between adults and infants were found in the neuronal apoptotic indexes of the Cu (28.2±16.3% vs. 6.9±8.7%), MedVe (24.7±15.0% vs. 11.3±11.4%), NTS (11.2±11.2% vs. 2.3±2.4%), DMNV (6.8±8.5% vs. 0.1±0.2%) and XII (6.6±5.7% vs. 0.1±0.2%). Differences in neuronal apoptotic index were also statistically significant among nuclei, those with higher neuronal apoptotic indexes being the Cu, MedVe and NSTT. In the medullary nuclei PDE4B and PDE4D mRNA expression was abundant and distributed not only in neuronal cells, but also in glial cells, especially on and around blood vessels. The hybridization signals for PDE4B and PDE4D mRNAs in the AP were stronger than in any other nucleus considered. They were also found in vomiting-related nuclei such as NTS and DMNV. In the carotid body, no AM, NTR1, and NCAM immunoreactivities were visible in type II cells. Anti-NTR1 and -NCAM immunohistochemistries showed positivity in 45.6 ± 9.2% and 78.3 ± 7.2% of adult type I cells, respectively. Higher percentages of positive type I cells were found in adult than foetal subjects for anti-AM (32.3 ± 7.7% vs 11.8 ± 2.7%, P<0.001), -ERK (32.3 ± 7.7% vs 11.8 ± 2.7%, P<0.001), -pERK (32.3 ± 7.7% vs 11.8 ± 2.7%, P<0.001), -AKT (32.3 ± 7.7% vs 11.8 ± 2.7%, P<0.001) and -pAKT (32.3 ± 7.7% vs 11.8 ± 2.7%, P<0.001) immunohistochemistries. DISCUSSION – The higher nuclear volumes and lower neuronal densities in adults may be ascribed to postnatal development of the neuropil and microvascularization. The higher apoptotic indexes in adults indicate higher resistance of infant neuronal populations to terminal hypoxic-ischaemic injury or post-mortem changes. Moreover, nuclei with higher apoptotic indexes are located in the lateral medullary tegmentum and share the same vascular supply from the posterior inferior cerebellar artery, suggesting different characteristics of survival on vascular basis. High PDE4 expression in the AP suggests that cAMP signaling modification could mediate the emetic effects of PDE4 inhibitors in human brainstem. Immunohistochemical findings in the carotid body suggest that AM and NT may play a role in the regulation of chemoreceptor discharge. The high expression level of NCAM in the carotid body indicates a role in regulating adhesion between type I cells. It may be hypothetized that the ERK and AKT signalling pathways in the carotid body are activated by neuromodulator/neurotrophic factors and plays a role in producing long-term cellular modifications. The lower expression of AM, ERK/pERK, and AKT/pAKT in foetuses may be ascribed to the absence of pulmonary respiration with lack of regulatory role of the carotid body during the prenatal period." @default.
• W179686039 created "2016-06-24" @default.
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• W179686039 date "2009-01-01" @default.
• W179686039 modified "2023-09-27" @default.
• W179686039 title "Studio neuroanatomico dei centri di regolazione cardiorespiratoria: bulbo encefalico e glomo carotideo" @default.
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