title: Monoaminergic control of spinal locomotor networks in SOD1G93A newborn mice.
abstract: Mutations in the gene that encodes Cu/Zn-superoxide dismutase (SOD1) are the cause of approximately 20% of familial forms of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. While ALS symptoms appear in adulthood, spinal motoneurons exhibit functional alterations as early as the embryonic and postnatal stages in the murine model of ALS, the SOD1 mice. Monoaminergic - i.e., dopaminergic (DA), serotoninergic (5-HT), and noradrenergic (NA) - pathways powerfully control spinal networks and contribute significantly to their embryonic and postnatal maturation. Alterations in monoaminergic neuromodulation during development could therefore lead to impairments in the motoneuronal physiology. In this study, we sought to determine whether the monoaminergic spinal systems are modified in the early stages of development in SOD1 mice. Using a post-mortem analysis by high performance liquid chromatography (HPLC), monoaminergic neuromodulators and their metabolites were quantified in the lumbar spinal cord of SOD1 and wild-type (WT) mice aged one postnatal day (P1) and P10. This analysis underscores an increased content of DA in the SOD1 lumbar spinal cord compared to that of WT mice but failed to reveal any modification of the other monoaminergic contents. In a next step, we compared the efficiency of the monoaminergic compounds in triggering and modulating fictive locomotion in WT and SOD1 mice. This study was performed in P1-P3 SOD1 mice and age-matched control littermates using extracellular recordings from the lumbar ventral roots in the in vitro isolated spinal cord preparation. This analysis revealed that the spinal networks of SOD1(G93A) mice could generate normal locomotor activity in the presence of NMA-5-HT. Interestingly, we also observed that SOD1 spinal networks have an increased sensitivity to NA compared to WT spinal circuits but exhibited similar DA responses.
authors: CNRS, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR5287, Université de Bordeaux Bordeaux, France.
authors: Léa
authors: L
authors: Milan
authors: CNRS, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR5287, Université de Bordeaux Bordeaux, France.
authors: Grégory
authors: G
authors: Barrière
authors: Institut des Maladies Neurodégénératives, Université de Bordeaux Bordeaux, France.
authors: Philippe
authors: P
authors: De Deurwaerdère
authors: CNRS, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR5287, Université de Bordeaux Bordeaux, France.
authors: Jean-René
authors: JR
authors: Cazalets
authors: CNRS, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR5287, Université de Bordeaux Bordeaux, France.
authors: Sandrine S
authors: SS
authors: Bertrand
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015306:Biogenic Monoamines / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D066298:In Vitro Techniques; D008124:Locomotion / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: ALS; HPLC; dopamine; extracellular recordings; fictive locomotion; noradrenaline; serotonin; spinal cord