Altered peripheral myelination in mice lacking GABAB receptors.
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.
Magnaghi
Valerio
V
Department of Endocrinology and Centre of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milan, Italy. valerio.magnaghi@unimi.it
Ballabio
Marinella
M
Camozzi
Francesca
F
Colleoni
Mariapia
M
Consoli
Antonio
A
Gassmann
Martin
M
Lauria
Giuseppe
G
Motta
Marcella
M
Procacci
Patrizia
P
Trovato
Anna Elisa
AE
Bettler
Bernhard
B
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
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