(1)H NMR-based metabolomics approach for exploring urinary metabolome modifications after acute and chronic physical exercise.

Metabolomics is a comprehensive method for metabolite assessment that involves measuring the overall metabolic signature of biological samples. We used this approach to investigate biochemical changes due to acute and chronic physical exercise. Twenty-two women using identical oral contraceptives were segregated into an untrained (n = 10) or trained (n = 12) group depending on their physical training background. The subjects performed two exercises in a randomized order: a prolonged exercise test (75% of their VO(2 max) until exhaustion) and a short-term, intensive exercise test (short-term, intensive exercise anaerobic test). Urine specimens were collected before and 30 min after each test. The samples were analyzed by (1)H NMR spectroscopy, and multivariate statistical techniques were utilized to process the data. Distinguishing characteristics were observed only in the urine profiles of specimens collected before vs. 30 min after the short-term, intensive exercise test. The metabolites responsible for such changes were creatinine, lactate, pyruvate, alanine, beta-hydroxybutyrate, acetate, and hypoxanthine. In both groups, the excretion of lactate, pyruvate, alanine, beta-hydroxybutyrate, and hypoxanthine increased similarly after the completion of the short-term, intensive exercise test (p < 0.03). However, acetate excretion increased to a lesser extent in trained than in untrained subjects (p < 0.05). In conclusion, metabolomics is a promising tool in order to gain insight into physiological status and to clarify the changes induced by short-term, intense physical exercise.

[Pathophysiological, molecular and metabolic changes at the neuromuscular junction and the peripheral nerve after central nervous system lesions in humans]. / Caractérisation physiopathologique, moléculaire et métabolique de la jonction neuromusculaire et du nerf périphérique après lésion du système nerveux central chez l'homme.

From the elaborate information processing that takes place in the brain to the contraction of skeletal muscles, the neurotransmission pathways involve, at least in part, (1) in tissue, Na+, K+-ATPase electrogenesis making action potential (AP) propagation possible and (2) in the cell, the synthesis, maturation, and renewal of an amazing number of molecules concentrated at the neuromuscular junction (NMJ). Our aim is to clarify CNS and peripheral nerve system (PNS) interactions by determining whether the partial motor recovery sometimes observed after a lesion of the first motoneuron is related to (1) changes in active transportation of the ions in peripheral nerve and/or muscle and (2) morphological and/or molecular changes at the NMJ, illustrating a dysfunction. Peripheral nerve surgery is proposed to some spastic patients who have recovered partially after CNS lesions to improve their gait. During these surgical procedures, the nerve and muscle samples that are usually resected can be collected and analyzed. Here, we report on eight patients who showed strictly similar motor recovery 2 years after massive CNS lesions and who underwent a selective tibial neurotomy for a spastic equinus foot. In these eight spastic patients, we performed a pathophysiological, molecular, and metabolic study of their neuromuscular junctions and peripheral nerves to characterize the dysfunction of the neuromuscular transmission after a permanent CNS injury.

[Toward a metabolic approach of the central pattern generator concept in a spinal rat model]. / Vers une approche métabolique du centre locomoteur autonome chez l'animal: le modèle d'hémisection médullaire chez le rat.

It has been shown that the onset of a central nervous system lesion in the rat results in morphological modifications of the peripheral nerves and the underlying neuromuscular junctions, without suggesting a functional correlation between recuperation of motor functions and sublesional metabolic activity. Using double lesion localization (T2 and T6) in a spinal rat model has nevertheless pointed out the functional importance of the T2-T6 metameric interval in the reinnervation phenomena observed, raising the problem of spinal generation in locomotor movements. Motivated by electrophysiological data that have given support to the concept of an anatomic substrate for these intramedullary rhythm generators, we attempted to establish a relation between the functional recuperation possible after a central nervous system lesion and modifications within the metabolism of the underlying neuromuscular system. We notably focused on Na/K-ATPase, whose crucial role in neuromuscular transmission has been evidenced. This paper proposes to demonstrate the involvement in the mechanisms of metabolic regulation after trans-synaptic denervation, i.e., a central nervous system lesion. Our study includes the Na/K-ATPase activity analysis on the sublesional peripheral nerve and the combined analysis of the expression of different RNA messengers within the corresponding muscle groups. We have also investigated the spatiotemporal organization of the compensating processes of the nerves underlying the lesion using magnetic resonance spectroscopy.

[Morphological study of CNS lesions and the consequences on rat neuromuscular junction and peripheral nerve using confocal laser scanning microscopy and Koelle's technique]. / Existe-t-il un retentissement sur la jonction neuromusculaire de rat lors de lésions du système nerveux central ? Etude morphologique en microscopie confocale et technique de Koelle.

STATE OF THE ART: In humans, it is currently believed that peripheral nerves remain intact after central nervous system (CNS) injuries. This should lead us to observe a lack of amyotrophy in the peripheral projection areas of CNS damage. Nevertheless, the appearance of amyotrophy, described as underuse amyotrophy, is common in victims of CNS injury. Its pathophysiology remains poorly understood and is currently being debated. Amyotrophy could result directly from the structural deterioration of a nervous fiber in the muscular area corresponding to the CNS injury caused by neuromuscular junction (NMJ) changes. AIMS OF THIS STUDY: The aims of this study were to assess the repercussions of a CNS injury on the NMJ and peripheral nerve complex and to evaluate the involvement of peripheral nerves and NMJs in plasticity. METHODOLOGY: Peripheral nerve and muscle biopsies were collected from a group of 35 female Wistar rats that had previously undergone a thoracic spinal cord hemisection (15 rats at the T2 level (group 1), 15 rats at the T6 level (group 2), and 5 matched rats used as controls). We studied the localization and expression of the NMJ molecular components in muscle specimens by immunohistochemistry using confocal microscopy. We also searched for signs of nerve and muscle degeneration using light and electron microscopy. RESULTS: We observed nonpathologic NMJs coexisting with completely denervated and partially reinnervated NMJs. We also found characteristics of embryonic behavior in rat axons secondary to axonal caliber distortions. Some authors associate this decrease in axonal activity with physiological denervation. CONCLUSION: This project was designed to improve the understanding of the mechanisms involved in the interactions between the first and second motoneurons after different types of CNS injuries, with variable functional repercussions. Our results strongly suggest that CNS injuries lead to both morphological and functional repercussions at the NMJ and the peripheral nerve.