The role of serotonin in respiratory function and dysfunction

Hilaire, Gérard; Voituron, Nicolas; Menuet, Clément; Ichiyama, Ronaldo M.; Subramanian, Hari H.; Dutschmann, Mathias

doi:10.1016/j.resp.2010.08.017

Cited by 145 publications

(137 citation statements)

References 191 publications

(219 reference statements)

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“…5-HT neurons in the medullary raphe (raphe magnus [RMg]; raphe pallidus [RPa]; raphe obscurus [ROb]) have been shown to be connected with the respiratory network [5,6,13,18,26,50,64] and may play an important role in the central-peripheral chemoreceptor interaction [15]. Data obtained from a variety of experimental approaches and different animal models, including genetically modified animals [24,28], support a role for the medullary raphe and specifically 5-HT neurons in central chemoreception [7,22,23].…”

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confidence: 99%

Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

Silva

Giusti

Benedetti

et al. 2011

Pflugers Arch - Eur J Physiol

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Serotonergic (5-HT) neurons in the nucleus raphe obscurus (ROb) are involved in the respiratory control network. However, it is not known whether ROb 5-HT neurons play a role in the functional interdependence between central and peripheral chemoreceptors. Therefore, we investigated the role of ROb 5-HT neurons in the ventilatory responses to CO₂ and their putative involvement in the central-peripheral CO₂ chemoreceptor interaction in unanaesthetised rats. We used a chemical lesion specific for 5-HT neurons (anti-SERT-SAP) of the ROb in animals with the carotid body (CB) intact or removed (CBR). Pulmonary ventilation (V (E)), body temperature and the arterial blood gases were measured before, during and after a hypercapnic challenge (7% CO₂). The lesion of ROb 5-HT neurons alone (CB intact) or the lesion of 5-HT neurons of ROb+CBR did not affect baseline V (E) during normocapnic condition. Killing ROb 5-HT neurons (CB intact) significantly decreased the ventilatory response to hypercapnia (p < 0.05). The reduction in CO₂ sensitivity was approximately 15%. When ROb 5-HT neurons lesion was combined with CBR (anti-SERT-SAP+CBR), the V (E) response to hypercapnia was further decreased (-31.2%) compared to the control group. The attenuation of CO₂ sensitivity was approximately 30%, and it was more pronounced than the sum of the individual effects of central (ROb lesion; -12.3%) or peripheral (CBR; -5.5%) treatments. Our data indicate that ROb 5-HT neurons play an important role in the CO₂ drive to breathing and may act as an important element in the central-peripheral chemoreception interaction to CO₂ responsiveness.

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mentioning

confidence: 99%

Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

Silva

Giusti

Benedetti

et al. 2011

Pflugers Arch - Eur J Physiol

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“…Medullary 5-HT neurons project to respiration-related neurons in the ventral medulla and affect respiratory patterns 2 . They act as sensors of CO 2 and pH 3 and enhance ventilatory responses to hypercapnia 4 .…”

Section: Originalmentioning

confidence: 99%

Early Onset of Ventilatory and Airway Response to Hypercapnia is Mediated by Medullary 5-HT<sub>1A</sub> Receptors in Infant Rats

Matsudaira

Kanamaru

Iizuka

et al. 2014

Showa Univ J Med Sci

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: Medullary 5-hydroxytryptamine 5-HT neurons are involved in ventilatory responses to hypercapnia. Underdeveloped medullary 5-HT neurons and reduced 5-HT 1A receptor binding activity in the dorsomedial medulla oblongata DMM have been found in infants with sudden infant death syndrome SIDS . The DMM includes the solitary tract nucleus, which receives primary afferent inputs from the lung, and the hypoglossal nucleus, which affects genioglossal muscle tone. We hypothesized that hypercapnia would elicit 5-HT release in the DMM and that local 5-HT 1A receptors would affect ventilatory and airway responses to hypercapnia. This hypothesis was investigated in unanesthetized infant Wistar rats by microdialysis of the DMM coupled with double-chamber plethysmography. After microdialysis probe placement, the rats were acclimatized to the chamber for over 5 h, and arti cial cerebrospinal uid aCSF or a 5-HT 1A receptor antagonist, WAY-100635, was then perfused into the DMM, and extracellular fluid was collected. Respiratory ow curves were recorded while the rats inhaled ve concentrations of CO 2 in O 2 for 10 min each 0 100 O 2 , 5 , 7 , 9 , and 0 again . 5-HT concentration was measured using high-performance liquid chromatography with electrochemical detection. 5-HT release in the DMM and hypercapnic ventilatory and airway responses increased dose dependently with CO 2 concentration during both aCSF and WAY-100635 perfusion, with no difference between groups. However, early-onset ventilatory and airway responses to hypercapnia were signicantly delayed or reduced by WAY-100635 perfusion in the DMM. These results suggest that 5-HT release in the DMM is dependent on hypercapnia, while early ventilatory and airway responses to hypercapnia are mediated by 5-HT 1A receptors in the DMM. Blunted early onset of hypercapnic ventilatory and airway responses may be one cause of SIDS.

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“…La création de modèles de souris transgéniques a incité également les chercheurs à adapter l'approche de Suzue à la souris, afin d'étudier in vitro le développement du CPB de souris dont un gène et un seul a été inactivé. Couplées à des approches pharmacologiques, ces études ont révélé que les systèmes à sérotonine (5-HT) [15,16] et à catécholamine [17,18] modulent le fonctionnement du CPB, et que l'altération de ces systèmes affecte la maturation de ce dernier [19][20][21]. À Gif-sur-Yvette (France), l'utilisation combinée de l'électrophysiologie et de l'imagerie calcique in vitro a révélé que l'émer-gence fonctionnelle du CPB est précédée par celle du groupe rétrotrapézoïde/parafacial (RTN/pFRG), une structure cruciale pour la réponse respiratoire à l'hypercapnie chez l'adulte.…”

Section: Rôle Crucial Du Complexe De Pré-bötzinger Dans L'automatismeunclassified

“…En effet, la maturation et le fonctionnement du CPB sont modulés par les systèmes monoaminergiques [15][16][17][18][19][20][21] ; les gènes qui modifient ces systèmes affectent indirectement le CPB. Ainsi, l'inactivation chez la souris de l'enzyme MAOA-A (monoamine oxydase A) [15] ou du gène Phox2a (paired mesoderm homeobox protein 2A) [17] ou du gène c-Ret (rearranged during transfection) [18] altère les systèmes monoaminergiques et, par voie de conséquence, le CPB et la respiration ; des anomalies monoaminergiques pourraient contribuer à certains cas de mort subite du nourrisson [16,[19][20][21]. L'inactivation du gène Necdin, qui affecte les systèmes à 5-HT, induit un rythme respiratoire irrégulier, de fréquentes apnées et une hyposensibilité à l'hypoxie et l'hypercapnie.…”

Section: Aspects Cliniquesunclassified