title: Lack of adenylate cyclase 1 (AC1): consequences on corticospinal tract development and on locomotor recovery after spinal cord injury.
abstract: Cyclic AMP (cAMP) signalling pathways are involved in axonal growth and regeneration. The calcium-calmodulin- stimulated adenylate cyclase 1 (AC1), a regulator of cAMP levels, is strongly expressed in the corticospinal motor neurons (CSMN) in cerebral cortex layer V during development, but its role in the development of the corticospinal tract (CST) is unknown. Here, we analyse the organization of the CST pathway using anterograde and retrograde tracers in the barrelless (brl) mouse that carries an inactivating mutation of the AC1 gene. We show that in brl mice the general organization of the CST is normal but there is an increase in the number of axons in the ipsilateral contingent in the dorsal and ventral medial funiculi of the cervical spinal cord. The density of CSMN in layer V of the motor cortex is increased in brl compared to wild-type mice. Thus, lack of AC1 likely perturbs late phases of CSMN and CST development. Next, we examine the motor recovery after a spinal cord injury (SCI). We find that brl mice show enhanced locomotor functions as assessed by the BMS (Basso mouse scale) as early as 6h and up to 6 weeks after SCI, indicating a smaller responsiveness of brl mice to SCI. It is therefore possible that developmental effects on motor systems might decrease the locomotor effects consecutive to a SCI. This point is particularly important with regards to the use of transgenic animals for testing SCI recovery.
authors.affiliation: Lab Pharmacology, Neurobiology & Behavior (URAC-37), Cadi Ayyad University, Faculty of Sciences Semlalia, Marrakech, Morocco; Inserm, UMR-S 839, Paris, France; UPMC, Univ Paris 06, 75005 Paris, France; Institut du Fer a Moulin, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Nait Taleb Ali
authors.affiliation: UPMC, Univ Paris 06, 75005 Paris, France; UPMC, Univ Paris 06, 75005 Paris, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Morel
authors.affiliation: UPMC, Univ Paris 06, 75005 Paris, France; UPMC, Univ Paris 06, 75005 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Doulazmi
authors.affiliation: Inserm, UMR-S 839, Paris, France; UPMC, Univ Paris 06, 75005 Paris, France; Institut du Fer a Moulin, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Scotto-Lomassese
authors.affiliation: Inserm, UMR-S 839, Paris, France; UPMC, Univ Paris 06, 75005 Paris, France; Institut du Fer a Moulin, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Gaspar
authors.affiliation: UPMC, Univ Paris 06, 75005 Paris, France; CNRS, UMR 7102, Université Pierre et Marie Curie, 9 Quai Saint Bernard, Paris 75005, France. Electronic address: isabelle.dusart@upmc.fr.
authors.forename: I
authors.initials: I
authors.lastname: Dusart
authors.affiliation: Lab Pharmacology, Neurobiology & Behavior (URAC-37), Cadi Ayyad University, Faculty of Sciences Semlalia, Marrakech, Morocco.
authors.forename: M
authors.initials: M
authors.lastname: Bennis
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000818:Animals; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000166:cytology; D011712:Pyramidal Tracts / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1
keywords: Adenylate cyclase 1; Barrelless mice; Corticospinal tract; Spinal cord injury