Role of BDNF in the dorsal vagal complex of the Wistar rat and its implication in the swallowing reflex

National audienc

Role of BDNF in the dorsal vagal complex of the Wistar rat and its implication in the swallowing reflex

International audienc

Growth restriction induced by chronic prenatal hypoxia affects breathing rhythm and its pontine catecholaminergic modulation.

International audienceImpaired transplacental supply of oxygen leads to intra uterine growth restriction, one of the most important cause of perinatal mortality and respiratory morbidity. The breathing rhythm depends on the central respiratory network modulated by catecholamines. We investigated the impact of growth restriction, using prenatal hypoxia, on the central respiratory-like rhythm and on its catecholaminergic modulation after birth. At birth the respiratory frequency was increased and confirmed in, en bloc medullary preparations where the frequency of the fourth cervical (C4) ventral root discharge was increased, and in slice preparations containing the prebötzinger complex with an increased inspiratory rhythm. The inhibition of the C4 burst discharge observed in ponto-medullary preparation was stronger in the growth restricted group. These results cannot be directly linked by the tyrosine hydroxylase (TH) activity increase of A1/C1 and A2/C2 cell groups in the medulla since blocking the α-adrenergic receptors 1 and 2 does not abolish the difference between both groups. However in ponto-medullary preparation, the stronger inhibition of C4 burst discharge is probably supported by an increased inhibition of A5, a respiratory rhythm inhibitor pontine group of neurons, displaying an increased TH activity because blocking 2 adrenergic receptors abolished the difference between the two groups. Altogether, these results indicate that growth restriction leads to a perturbation of the breathing frequency, which finds, at least in part, its origin in the modification of the catecholaminergic modulation of the central breathing network

Developmental plasticity of the carotid chemoafferent pathway in rats that are hypoxic during the prenatal period.

International audienceThe chemoreflex pathway undergoes postnatal maturation, and the perinatal environment plays a critical role in shaping respiratory control system. We investigated the role of prenatal hypoxia on the maturation of the chemoreflex neural circuits regulating ventilation in rat. Effects of hypoxia (10% O(2)) from the 5th to the 20th day of gestation were studied on male offspring at birth and on postnatal days 3, 7, 21 and 68. Maturation of the respiratory control system was assessed by in vivo tyrosine hydroxylase (TH) activity measurement in peripheral chemoreceptors (carotid bodies, petrosal ganglia), and in brainstem catecholaminergic cell groups (A(2)C(2)c and A(1)C(1) areas in the medulla, A(5) and A(6) areas in the pons). Resting ventilation and ventilatory response to hypoxia were evaluated as functional sequelae. In peripheral structures, prenatal hypoxia reduced TH activity within the first postnatal week and enhanced it later. In contrast, in central areas, prenatal hypoxia upregulated TH activity within the first postnatal week and downregulated it later. The in vivo TH activity impairment is therefore tissue specific, with an opposite effect on the peripheral and central neural circuits. A shift of the effect of prenatal hypoxia occurred between 1 and 3 weeks, indicating a postnatal temporal effect of prenatal hypoxia. An important period in the development of the chemoafferent pathway occurred between the first and the third postnatal week. Functionally, prenatal hypoxia impaired resting ventilation and ventilatory response to hypoxia. The alterations of the catecholaminergic components of the chemoafferent pathway resulting from prenatal hypoxia might contribute to impair postnatal respiratory behaviour

The M-current works in tandem with the persistent sodium current to set the speed of locomotion

International audienceThe central pattern generator (CPG) for locomotion is a set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current (IM): a subthreshold noninactivating outward current blocked by 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and enhanced by N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA73). Immunostaining and mutant mice highlight an important role of Kv7.2-containing channels in mediating IM. Pharmacological modulation of IM regulates the emergence and the frequency regime of both pacemaker and CPG activities and controls the speed of locomotion. Computational models captured these results and showed how an interplay between IM and INaP endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how IM and INaP work in tandem to set the speed of locomotion

Deficits of brainstem and spinal cord functions after neonatal hypoxia–ischemia in mice

International audienc

Task2 potassium channels set central respiratory CO2 and O2 sensitivity

Task2 K+ channel expression in the central nervous system is surprisingly restricted to a few brainstem nuclei, including the retrotrapezoid (RTN) region. All Task2-positive RTN neurons were lost in mice bearing a Phox2b mutation that causes the human congenital central hypoventilation syndrome. In plethysmography, Task2−/− mice showed disturbed chemosensory function with hypersensitivity to low CO2 concentrations, leading to hyperventilation. Task2 probably is needed to stabilize the membrane potential of chemoreceptive cells. In addition, Task2−/− mice lost the long-term hypoxia-induced respiratory decrease whereas the acute carotid-body-mediated increase was maintained. The lack of anoxia-induced respiratory depression in the isolated brainstem–spinal cord preparation suggested a central origin of the phenotype. Task2 activation by reactive oxygen species generated during hypoxia could silence RTN neurons, thus contributing to respiratory depression. These data identify Task2 as a determinant of central O2 chemoreception and demonstrate that this phenomenon is due to the activity of a small number of neurons located at the ventral medullary surface

Deficits of brainstem and spinal cord functions after neonatal hypoxia–ischemia in mice

International audienc

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed