title: Altered peripheral myelination in mice lacking GABAB receptors.
abstract: Emerging evidence implicates gamma-aminobutyric acid type B (GABA(B)) receptors in peripheral nervous system (PNS) functions. In order to elucidate which biochemical, morphological and functional parameters of peripheral nerve fibers depend on GABA(B) receptors we studied GABA(B1)-deficient mice, which are devoid of functional GABA(B) receptors. Here, we show that GABA(B1)-deficient mice exhibit morphological and molecular changes in peripheral myelin, including an increase in the number of irregular fibers and increases in the expression levels of the myelin proteins PMP22 and P0. Moreover, the number of small myelinated fibers and small neurons of the lumbar dorsal root ganglia is higher in GABA(B1)-deficient mice than in wild-type littermates. We further show that GABA(B1)-deficient mice exhibit gait alterations and reduced allodynia. In summary, our findings implicate GABA(B) receptors in the PNS myelination process and raise the possibility that PNS alterations contribute to the sensory phenotypes of GABA(B1)-deficient mice.
authors.affiliation: Department of Endocrinology and Centre of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. valerio.magnaghi@unimi.it
authors.forename: Valerio
authors.initials: V
authors.lastname: Magnaghi
authors.forename: Marinella
authors.initials: M
authors.lastname: Ballabio
authors.forename: Francesca
authors.initials: F
authors.lastname: Camozzi
authors.forename: Mariapia
authors.initials: M
authors.lastname: Colleoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Consoli
authors.forename: Martin
authors.initials: M
authors.lastname: Gassmann
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.forename: Marcella
authors.initials: M
authors.lastname: Motta
authors.forename: Patrizia
authors.initials: P
authors.lastname: Procacci
authors.forename: Anna Elisa
authors.initials: AE
authors.lastname: Trovato
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005684:Gait / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008854:Microscopy, Electron / Q000379:methods; D018993:Myelin P0 Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism / Q000648:ultrastructure; D010147:Pain Measurement; D017933:Peripheral Nervous System / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000172:deficiency*; D012584:Sciatic Nerve / Q000378:metabolism / Q000648:ultrastructure; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D018993:Myelin P0 Protein; D009185:Myelin Proteins; C489545:Pmp22 protein, mouse; D018080:Receptors, GABA-B; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse; D015740:Calcitonin Gene-Related Peptide