the-c-fos-protein-immunohistological-detection-useful-tool-as-marker

The c-FOS Protein Immunohistological Detection: A Useful Tool As a Marker of Central Pathways Involved in Specific Physiological Responses <em>In Vivo</em> and <em>Ex Vivo</em>

Many studies seek to identify and map the brain regions involved in specific physiological regulations. The proto-oncogene c-fos, an immediate early gene, ...

University Paris 13

Laboratory of Excellence GR-Ex

The N-Methyl-d-Aspartate (NMDA) receptors - neuronal nitric oxide synthase (nNOS) pathway is involved in the ventilatory response to hypoxia. The objective was to assess the possible effect of erythropoietin deficiency and chronic exposure to hypoxia on this pathway during ventilatory response to acute hypoxia. Wild-type (WT) and erythropoietin-deficient (Epo-TAg(h)) male mice were exposed (14 days) either to hypobaric hypoxia (Pb = 435 mmHg) or to normoxia. The ventilation was measured at 21% or 8% O2 after injection of vehicle (NaCl), nNOS inhibitor (SMTC) or NMDA receptor antagonist (MK-801). Nitric oxide production and the expression of NMDA receptor and nNOS were assessed by real-time RT-PCR and Western blot analyses in the medulla. At rest, Epo-TAg(h) mice displayed normal ventilatory parameters at 21% O2 but did not respond to acute hypoxia despite a larger expression of NMDA receptors and nNOS in the medulla. Ventilatory acclimatization to hypoxia was observed in WT but was absent in Epo-TAg(h) mice. nNOS inhibition blunted the hypoxic ventilatory acclimatization of WT mice without any effect in Epo-TAg(h) mice. Acute hypoxic ventilatory response (HVR) was increased after chronic hypoxia in WT but remained unchanged in Epo-TAg(h) mice. Ventilatory response to acute hypoxia was modified by MK-801 injection in WT and Epo-TAg(h) mice. The results confirm that adequate erythropoietin level is necessary to obtain an appropriate HVR and a significant ventilatory acclimatization to hypoxia. Furthermore, erythropoietin plays a potential catalyzing role in the NMDA-NO central pathway during the ventilatory response and acclimatization to hypoxia.

Catalyzing role of erythropoietin on the nitric oxide central pathway during the ventilatory responses to hypoxia.

The highland "plateau Pika" is considered to be adapted to chronic hypoxia. We hypothesized that glutamate N-methyl-D-aspartate (NMDA) and non-NMDA receptors, nitric oxide (NO) synthase, and serotonin are involved in hypoxic ventilatory response (HVR) in Pikas. We tested the effects of NMDA (memantine) and non-NMDA receptors (DNQX) antagonists, NO synthase inhibitor (L-NAME), and selective serotonin reuptake inhibitors (fluoxetine) on ventilation and HVR in Pikas. Ventilatory parameters were measured before and after drug (or vehicle) injections in conscious Pikas at their natural living altitude (PIO2 86 mmHg) and after a hypoxic challenge (PIO2 57 mmHg, 3 min) to assess the influence of peripheral chemoreceptor on HVR. Minute ventilation (VI) and tidal volume (Vt) increased during hypoxic challenge after vehicle injection, whereas the Ti/Ttot ratio remained unchanged. The increase in VI and Vt observed with vehicle at PIO2-57, when compared with PIO2-86, was inhibited after memantine and fluoxetine injection, whereas the DNQX injection increased HVR. At PIO2-57, L-NAME induced an increase in the Ti/Ttot ratio when compared with vehicle. Therefore, the glutamate through NMDA-R/AMPA receptor bindings and serotonin pathway are implicated at the peripheral chemoreceptor level in HVR in Pikas. However, NO influences the ventilatory pattern of Pikas at their habitual living altitude.

Role of glutamate and serotonin on the hypoxic ventilatory response in high-altitude-adapted plateau Pika.

The objective of this study was to compare the different ventilatory strategies that help in coping with hypoxic-hypercapnia environment among two species: use acclimated rats and plateau pikas (Ochotona curzoniae) that live in Tibetan plateaus, and have been well adjusted to high altitude. Arterial blood samples taken at 4100 m of elevation in acclimatized rats and adapted pikas revealed inter-species differences with lower hemoglobin and hematocrit and higher blood pH in pikas. A linear and significant increase in minute ventilation was observed in pikas, which help them to cope with hypoxic-hypercapnia. Pikas also displayed a high inspiratory drive and an invariant respiratory timing regardless of the conditions. Biochemical analysis revealed that N-methyl-D-aspartate receptor (NMDA) receptor gene and nNOS gene are highly conserved between rats and pikas, however pikas have higher expression of NMDA receptors and nNOS compared to rats at the brainstem level. Taken together, these results suggest that pikas have developed a specific ventilatory pattern supported by a modification of the NMDA/NO ventilatory central pathways to survive in extreme conditions imposed on the Tibetan plateaus. These physiological adaptive strategies help in maintaining a better blood oxygenation despite high CO2 concentration in burrows at high altitude.

Article	Year
Catalyzing role of erythropoietin on the nitric oxide central pathway during the ventilatory responses to hypoxia. Physiological reports\| PubMed ID: 24744892	2014
Role of glutamate and serotonin on the hypoxic ventilatory response in high-altitude-adapted plateau Pika. Respiratory physiology & neurobiology\| PubMed ID: 25890014	2015
Comparative ventilatory strategies of acclimated rats and burrowing plateau pika (Ochotona curzoniae) in response to hypoxic-hypercapnia. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology\| PubMed ID: 25988712	2015

Florine Jeton

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