title: Age-Related Changes in Pre- and Postsynaptic Partners of the Cholinergic C-Boutons in Wild-Type and SOD1G93A Lumbar Motoneurons.
abstract: Large cholinergic synaptic terminals known as C-boutons densely innervate the soma and proximal dendrites of motoneurons that are prone to neurodegeneration in amyotrophic lateral sclerosis (ALS). Studies using the Cu/Zn-superoxide dismutase (SOD1) mouse model of ALS have generated conflicting data regarding C-bouton alterations exhibited during ALS pathogenesis. In the present work, a longitudinal study combining immunohistochemistry, biochemical approaches and extra- and intra-cellular electrophysiological recordings revealed that the whole spinal cholinergic system is modified in the SOD1 mouse model of ALS compared to wild type (WT) mice as early as the second postnatal week. In WT motoneurons, both C-bouton terminals and associated M2 postsynaptic receptors presented a complex age-related dynamic that appeared completely disrupted in SOD1 motoneurons. Indeed, parallel to C-bouton morphological alterations, analysis of confocal images revealed a clustering process of M2 receptors during WT motoneuron development and maturation that was absent in SOD1 motoneurons. Our data demonstrated for the first time that the lamina X cholinergic interneurons, the neuronal source of C-boutons, are over-abundant in high lumbar segments in SOD1 mice and are subject to neurodegeneration in the SOD1 animal model. Finally, we showed that early C-bouton system alterations have no physiological impact on the cholinergic neuromodulation of newborn motoneurons. Altogether, these data suggest a complete reconfiguration of the spinal cholinergic system in SOD1 spinal networks that could be part of the compensatory mechanisms established during spinal development.
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Léa
authors: L
authors: Milan
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Gilles
authors: G
authors: Courtand
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Laura
authors: L
authors: Cardoit
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Frédérique
authors: F
authors: Masmejean
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Grégory
authors: G
authors: Barrière
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Jean-René
authors: JR
authors: Cazalets
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Maurice
authors: M
authors: Garret
authors: INCIA, Université de Bordeaux, CNRS UMR5287, Bordeaux, France.
authors: Sandrine S
authors: SS
authors: Bertrand
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; D010095:Oxotremorine; D013482:Superoxide Dismutase