Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: The Case of the Bulbospinal Respiratory Neurons

High cervical spinal cord injuries interrupt the bulbospinal respiratory pathways projecting to the cervical phrenic motoneurons resulting in important respiratory defects. In the case of a lateralized injury that maintains the respiratory drive on the opposite side, a partial recovery of the ipsilateral respiratory function occurs spontaneously over time, as observed in animal models. The rodent respiratory system is therefore a relevant model to investigate the neuroplastic and neuroprotective mechanisms that will trigger such phrenic motoneurons reactivation by supraspinal pathways. Since part of this recovery is dependent on the damaged side of the spinal cord, the present review highlights our current understanding of the anatomical neuroplasticity processes that are developed by the surviving damaged bulbospinal neurons, notably axonal sprouting and rerouting. Such anatomical neuroplasticity relies also on coordinated molecular mechanisms at the level of the axotomized bulbospinal neurons that will promote both neuroprotection and axon growth

Mécanismes moléculaires de la perception olfactive chez les vertébrés (identification et expression fonctionnelle de récepteurs olfactifs)

Le système olfactif soulève une des questions les plus fascinantes de la physiologie sensorielle. Comment peut-on discriminer plusieurs milliers de molécules odorantes ? Pour faire face à cette diversité d'informations, ce système neurosensoriel a adopté une stratégie de réception qui se distingue des autres sens en faisant appel à un grand répertoire de récepteurs couplés aux protéines-G dénomés récepteurs olfactifs. La connaissance de ces derniers est apparue incontournable pour comprendre les mécanismes moléculaires de la réception olfactive. Notre premier objectif a été d'identifier une vingtaine de nouveaux récepteurs olfactifs exprimés dans l'épithélium olfactif de deux vertébrés, le porc et la marmotte alpine. Dans une deuxième étape, assigner une fonction olfactive à ces récepteurs est une nécessité logique. Nous avons opté pour une stratégie d'expression dans des systèmes cellulaires hétérologues de mammifère et d'insecte. Nos premières expériences ont montré que l'expression des récepteurs olfactifs en cellule hétérologue est limitée dans l'adressage à la membrane. Pour contourner cette difficulté, nous avons réussi à améliorer l'expression membranaire en introduisant dans les séquences de récepteurs un peptide de signalisation. Les récepteurs exprimés dans des cellules de mammifère nous ont permis de mettre en évidence une interaction avec une protéine de transport des molécules odorantes (OBP). Nous avons obtenu une liaison entre une OBP de porc radiomarquée et l'un de nos récepteurs. De plus, en utilisant l'imagerie calcique, nous montrons que les cellules d'insectes infectées par des récepteurs olfactifs répondent à un mélange d'odorants. Les données actuelles et nos résultats sont discutés pour tenter de définir un modèle de la réception olfactive et pour envisager les applications industrielles qui peuvent être développées en s'inspirant de ce modèle biologiqueAIX-MARSEILLE1-BU Sci.St Charles (130552104) / SudocSudocFranceF

Neuroprotective and Neurorestorative Processes after Spinal Cord Injury: ă The Case of the Bulbospinal Respiratory Neurons

International audienceHigh cervical spinal cord injuries interrupt the bulbospinal respiratory ă pathways projecting to the cervical phrenic motoneurons resulting in ă important respiratory defects. In the case of a lateralized injury that ă maintains the respiratory drive on the opposite side, a partial recovery ă of the ipsilateral respiratory function occurs spontaneously over time, ă as observed in animal models. The rodent respiratory system is therefore ă a relevant model to investigate the neuroplastic and neuroprotective ă mechanisms that will trigger such phrenic motoneurons reactivation by ă supraspinal pathways. Since part of this recovery is dependent on the ă damaged side of the spinal cord, the present review highlights our ă current understanding of the anatomical neuroplasticity processes that ă are developed by the surviving damaged bulbospinal neurons, notably ă axonal sprouting and rerouting. Such anatomical neuroplasticity relies ă also on coordinated molecular mechanisms at the level of the axotomized ă bulbospinal neurons that will promote both neuroprotection and axon ă growth

Neuroplasticité post-lésionnelle des voies respiratoires bulbo-spinales après lésion unilatérale cervicale de la moelle épinière

Cette thèse a comme objectif l étude des processus de plasticité du réseau bulbo-spinal respiratoire après une lésion spinale cervicale unilatérale en C2, qui induit une interruption de la majorité des fibres respiratoires. Cette étude est réalisée par une approche de traçage de voies, couplée à une approche immunohistochimique, biochimique et électrophysiologique.La lésion latérale chronique induit dans la région sus-lésionnelle C1/C2 une diminution du nombre de fibres bulbo-spinales marquées et de la surface de la substance blanche. Nous observons cependant une augmentation du nombre de fibres repoussant dans la substance grise, y compris de terminaisons axonales, ainsi qu une augmentation du nombre de neurones respiratoires se projetant vers les noyaux phréniques en C3/C4. Suite à la lésion, une sous-population de neurones respiratoires axotomisés exprime des marqueurs de réponse post-lésionnelle.Ces processus de plasticité pourraient contribuer à la récupération fonctionnelle.The aim of this thesis was to study the anatomical and cellular plasticity processes of bulbospinal respiratory pathways after a unilateral cervical spinal injury C2, which leads to an interruption of the respiratory fibers. This study used an approach of anterograde and retrograde labeling, coupled with immunohistochemical, biochemical and electrophysiological methods.The chronic lateral lesion induced in sus-lesional area C1/C2 a decreased of number of bulbospinal fibers and a decreased white matter, but an increased number fibers sprouting in the gray matter, including axon terminals, and an increased number of respiratory neurons projecting to the phrenic nuclei in C3/C4. Following the lesion, a sub-population of axotomized respiratory neurons express markers of cell body post-lesion response. These processes of plasticity could contribute to functional recovery.AIX-MARSEILLE3-Bib. élec. (130559903) / SudocSudocFranceF

Extensive respiratory plasticity after cervical spinal cord injury in rats: Axonal sprouting and rerouting of ventrolateral bulbospinal pathways

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Modulation of the thermosensory system by oxytocin

Oxytocin (OT) is a neurohormone involved early in neurodevelopment and is implicated in multiple functions, including sensory modulation. Evidence of such modulation has been observed for di erent sensory modalities in both healthy and pathological conditions. This review summarizes the pleiotropic modulation that OT can exercise on an often overlooked sensory system: thermosensation. This system allows us to sense temperature variations and compensate for the variation to maintain a stable core body temperature. Oxytocin modulates autonomic and behavioral mechanisms underlying thermoregulation at both central and peripheral levels. Hyposensitivity or hypersensitivity for di erent sensory modalities, including thermosensitivity, is a common feature in autism spectrum disorder (ASD), recapitulated in several ASD mouse models. These sensory dysregulations occur early in postnatal development and are correlated with dysregulation of the oxytocinergic system. In this study, we discussed the potential link between thermosensory atypia and the dysregulation of the oxytocinergic system in ASD

Distortion Correction and Denoising of Light Sheet Fluorescence Images

International audienceLight Sheet Fluorescence Microscopy (LSFM) has emerged as a valuable tool for neurobiologists, enabling the rapid and high-quality volumetric imaging of mice brains. However, inherent artifacts and distortions introduced during the imaging process necessitate careful enhancement of LSFM images for optimal 3D reconstructions. This work aims to correct images slice by slice before reconstructing 3D volumes. Our approach involves a three-step process: firstly, the implementation of a deblurring algorithm using the work of K. Becker; secondly, an automatic contrast enhancement; and thirdly, the development of a convolutional denoising auto-encoder featuring skip connections to effectively address noise introduced by contrast enhancement, particularly excelling in handling mixed Poisson–Gaussian noise. Additionally, we tackle the challenge of axial distortion in LSFM by introducing an approach based on an auto-encoder trained on bead calibration images. The proposed pipeline demonstrates a complete solution, presenting promising results that surpass existing methods in denoising LSFM images. These advancements hold potential to significantly improve the interpretation of biological data

Neural Cell Adhesion Molecule, a New Cytoadhesion Receptor for Plasmodium falciparum-Infected Erythrocytes Capable of Aggregation▿

The cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) to the endothelial cells lining the microvasculature, clogging the microvessels of various organs, is a key event in the pathogenesis of certain severe forms of malaria, such as cerebral malaria and pulmonary edema. Studies aiming to identify possible correlations between the severity of clinical cases and the presence of particular cytoadhesion phenotypes have been largely unsuccessful. One of the possible reasons for this failure is that some of the key receptors and/or mechanisms involved have yet to be identified. By combining IE selection, cell transfection, and adhesion inhibition assays, we identified a new cytoadhesion receptor, neural cell adhesion molecule (NCAM). NCAM is a member of the immunoglobulin superfamily and has nonpolysialylated and polysialylated isoforms, the latter being rare in adults. The nonpolysialylated form is present on the surfaces of endothelial cells in the microvessels of various organs in which IE sequestration occurs. We found that multiphenotypic IEs interacted with nonpolysialylated NCAM and with another, as yet unidentified receptor. These IEs also displayed cytoadhesion in flow conditions, presenting the unique ability to form adherent macroaggregates composed of hundreds of IEs. These features may act as virulence factors, increasing the capacity of IEs to clog microvessels via receptor synergy and macroaggregate formation, thereby facilitating the pathogenesis of severe forms of malaria

Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling

Leptin is an adipocyte-derived hormone that controls energy balance by acting primarily in the CNS, but its action is lost in common forms of obesity due to central leptin resistance. One potential mechanism for such leptin resistance is an increased hypothalamic expression of Suppressor of cytokine signaling 3 (Socs3), a feedback inhibitor of the Jak-Stat pathway that prevents Stat3 activation. Ample studies have confirmed the important role of Socs3 in leptin resistance and obesity. However, the degree to which Socs3 participates in the regulation of energy homeostasis in nonobese conditions remains largely undetermined. In this study, using adult mice maintained under standard diet, we demonstrate that Socs3 deficiency in the mediobasal hypothalamus (MBH) reduces food intake, protects against body weight gain, and limits adiposity, suggesting that Socs3 is necessary for normal body weight maintenance. Mechanistically, MBH Socs3-deficient mice display increased hindbrain sensitivity to endogenous, meal-related satiety signals, mediated by oxytocin signaling. Thus, oxytocin signaling likely mediates the effect of hypothalamic leptin on satiety circuits of the caudal brainstem. This provides an anatomical substrate for the effect of leptin on meal size, and more generally, a mechanism for how the brain controls short-term food intake as a function of the energetic stores available in the organism to maintain energy homeostasis. Any dysfunction in this pathway could potentially lead to overeating and obesity

Acute Neuromuscular Adaptation at the Spinal Level Following Middle Cerebral Artery Occlusion-Reperfusion in the Rat

International audienceThe purpose of the study was to highlight the acute motor reflex adaptation and to deepen functional deficits following a middle cerebral artery occlusion-reperfusion (MCAO-r). Thirty-six Sprague-Dawley rats were included in this study. The middle cerebral artery occlusion (MCAO; 120 min) was performed on 16 rats studied at 1 and 7 days, respectively (MCAO-D1 and MCAO-D7, n = 8 for each group). The other animals were divided into 3 groups: SHAM-D1 (n = 6), SHAM-D7 (n = 6) and Control (n = 8). Rats performed 4 behavioral tests (the elevated body swing test, the beam balance test, the ladder-climbing test and the forelimb grip force) before the surgery and daily after MCAO-r. H-reflex on triceps brachii was measured before and after isometric exercise. Infarction size and cerebral edema were respectively assessed by histological (Cresyl violet) and MRI measurements at the same time points than H-reflex recordings. Animals with cerebral ischemia showed persistent functional deficits during the first week post-MCAO-r. H-reflex was not decreased in response to isometric exercise one day after the cerebral ischemia contrary to the other groups. The motor reflex regulation was recovered 7 days post-MCAO-r. This result reflects an acute sensorimotor adaptation at the spinal level after MCAO-r