RT Journal Article
T1 Microbial Neuraminidase Induces a Moderate and Transient Myelin Vacuolation Independent of Complement System Activation.
A1 Granados-Durán, Pablo
A1 López-Ávalos, María Dolores
A1 Cifuentes, Manuel
A1 Pérez-Martín, Margarita
A1 Fernández-Arjona, María Del Mar
A1 Hughes, Timothy R
A1 Johnson, Krista
A1 Morgan, B Paul
A1 Fernández-Llebrez, Pedro
A1 Grondona, Jesús M
K1 C5a
K1 C6-deficient rats
K1 anti-C5
K1 brain
K1 complement system
K1 myelin vacuolation
K1 neuraminidase
K1 neuroinflammation
AB Aims: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage.Methods: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles. Neuronal death in the affected axonal tracts was assessed by Fluoro-Jade B and anti-caspase-3 staining. To evaluate the role of the complement, membrane attack complex (MAC) deposition on damaged bundles was analyzed using anti-C5b9. Rats ICV injected with the anaphylatoxin C5a were studied for myelin damage. In addition, NA-induced vacuolation was studied in rats with different degrees of complement inhibition: normal rats treated with anti-C5-blocking antibody and C6-deficient rats.Results: The stria medullaris, the optic chiasm, and the fimbria were the most consistently damaged axonal tracts. Vacuolation peaked 7 days after NA injection and reverted by day 15. Olig2+ cell number in the damaged tracts was unaltered, and neurodegeneration associated with myelin alterations was not detected. MAC was absent on damaged axonal tracts, as revealed by C5b9 immunostaining. Rats ICV injected with the anaphylatoxin C5a displayed no myelin injury. When the complement system was experimentally or constitutively inhibited, NA-induced myelin vacuolation was similar to that observed in normal rats.Conclusion: Microbial NA induces a moderate and transient myelin vacuolation that is not caused either by neuroinflammation or complement system activation.
PB Frontiers
SN 1664-2295
YR 2017
FD 2017-03-07
LK http://hdl.handle.net/10668/10986
UL http://hdl.handle.net/10668/10986
LA en
NO Granados-Durán P, López-Ávalos MD, Cifuentes M, Pérez-Martín M, Fernández-Arjona MDM, Hughes TR, et al. Microbial Neuraminidase Induces a Moderate and Transient Myelin Vacuolation Independent of Complement System Activation. Front Neurol. 2017;8:78. Published 2017 Mar 7.
NO This work was carried out with fundings from Ministerio de Economía y Competitividad (SAF2010-19087), Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (P11-CVI-07637), and Consejería de Salud, Junta de Andalucía (SAS 08-0029). The ultramicrotome Leica EM UC7 and the transmission electron microscope Geol JEM-1400 were acquired with FEDER funds of the European Union. The authors are grateful to Ms. Silvia Hernández Sánchez, Mrs. José Esteban Casares Mira, and Ms. Archana Jayanthi for their valuable technical help and Gregorio Martín Caballero and Adolfo Martínez Orellana for his help with the ultramicrotome and the transmission electron microscopy. The authors are grateful to Dr. Paul P. Tamburini from Alexion Pharmaceuticals for providing the functional blocking antibody against rat C5.
DS RISalud
RD Oct 13, 2025