title: A mouse model of familial amyotrophic lateral sclerosis expressing a mutant superoxide dismutase 1 shows evidence of disordered transport in the vasopressin hypothalamo-neurohypophysial axis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal, paralytic disorder that primarily affects motoneurons. By combining physiological and morphological approaches, we examined the effect of a murine superoxide dismutase 1 (SOD1) mutation (G86R), which induces neurological disorders resembling human familial ALS (FALS), on the arginine vasopressin (AVP) hypothalamo-neurohypophysial axis, an unmyelinated tract poor in neurofilaments. First, we observed that G86R mice progressively consumed more water than wild-type littermates. Furthermore, levels of plasma AVP and neurohypophysial AVP content were decreased in the SOD1 mutant mice, whereas the amount of hypothalamic AVP increased in an age-dependent manner. However, hypothalamic AVP mRNA levels were not significantly modified in these animals. At the ultrastructural level, we found that the neurohypophysis of G86R mice had a decreased number of neurosecretory axons. Conversely, the presence of large axon swellings was more pronounced in the SOD1 mutant mice. In addition, the size of neurosecretory granules was higher in G86R than in wild-type animals. All these findings strongly suggest that the FALS-associated SOD1 mutation injures the hypothalamo-neurohypophysial axis by provoking early, progressive disturbances in the axonal transport of neurosecretory products from neuronal perikarya to nerve terminals. This blockade could ultimately result in degeneration of the tract, as proposed for the myelinated, neurofilament-enriched motor axons affected by ALS.
authors.affiliation: Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS, Université Louis Pasteur, Strasbourg, France.
authors.forename: J L
authors.initials: JL
authors.lastname: González de Aguilar
authors.forename: J W
authors.initials: JW
authors.lastname: Gordon
authors.forename: F
authors.initials: F
authors.lastname: René
authors.forename: B
authors.initials: B
authors.lastname: Lutz-Bucher
authors.forename: P
authors.initials: P
authors.lastname: Kienlen-Campard
authors.forename: J P
authors.initials: JP
authors.lastname: Loeffler
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism*; D001370:Axonal Transport / Q000235:genetics; D001369:Axons / Q000145:classification / Q000378:metabolism / Q000648:ultrastructure; D001834:Body Water / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D009489:Neurosecretion; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D012333:RNA, Messenger; C000606290:SOD1 protein, human; D001127:Arginine Vasopressin; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1