title: Mice lacking GD3 synthase display morphological abnormalities in the sciatic nerve and neuronal disturbances during peripheral nerve regeneration.
abstract: The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neuroquímica, Rio de Janeiro, Rio de Janeiro, Brazil; Núcleo Multidisciplinar de Pesquisa em Biologia - NUMPEX-BIO, Universidade Federal do Rio de Janeiro, Pólo de Xerém, Duque de Caxias, Rio de Janeiro, Brazil.
authors.forename: Victor Túlio
authors.initials: VT
authors.lastname: Ribeiro-Resende
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neuroquímica, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Araújo Gomes
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neuroquímica, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Silmara
authors.initials: S
authors.lastname: de Lima
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neuroquímica, Rio de Janeiro, Rio de Janeiro, Brazil; Núcleo Multidisciplinar de Pesquisa em Biologia - NUMPEX-BIO, Universidade Federal do Rio de Janeiro, Pólo de Xerém, Duque de Caxias, Rio de Janeiro, Brazil.
authors.forename: Maiara
authors.initials: M
authors.lastname: Nascimento-Lima
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neurobiologia Celular e Molecular, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Michele
authors.initials: M
authors.lastname: Bargas-Rega
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neurobiologia Celular e Molecular, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcelo Felipe
authors.initials: MF
authors.lastname: Santiago
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neuroquímica, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ricardo Augusto de Melo
authors.initials: RA
authors.lastname: Reis
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Laboratório de Neuroquímica, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernando Garcia
authors.initials: FG
authors.lastname: de Mello
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D002452:Cell Count; D005260:Female; D005732:Gangliosides / Q000494:pharmacology; D055786:Gene Knockout Techniques; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D012584:Sciatic Nerve / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D012799:Sialyltransferases / Q000172:deficiency* / Q000235:genetics*
chemical_list: D005732:Gangliosides; D019012:Integrin beta1; C049132:9-O-acetyl-GD3 ganglioside; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase