Long-term production of BDNF and NT-3 induced by A91-immunization after spinal cord injury
Por:
Martinon, Susana, Garcia-Vences, Elisa, Toscano-Tejeida, Diana, Flores-Romero, Adrian, Rodriguez-Barrera, Roxana, Ferrusquia, Manuel, Hernandez-Munoz, Rolando E., Ibarra, Antonio
Publicada:
30 jun 2016
Resumen:
Background: After spinal cord (SC)-injury, a non-modulated immune
response contributes to the damage of neural tissue. Protective
autoimmunity (PA) is a T cell mediated, neuroprotective response induced
after SC-injury. Immunization with neural-derived peptides (INDP), such
as A91, has shown to promote-in vitro-the production of neurotrophic
factors. However, the production of these molecules has not been studied
at the site of injury.
Results: In order to evaluate these issues, we performed four
experiments in adult female Sprague-Dawley rats. In the first one, brain
derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)
concentrations were evaluated at the site of lesion 21 days after
SC-injury. BDNF and NT-3 were significantly increased in INDP-treated
animals. In the second experiment, proliferation of anti-A91 T cells was
assessed at chronic stages of injury. In this case, we found a
significant proliferation of these cells in animals subjected to
SC-injury + INDP. In the third experiment, we explored the amount of
BDNF and NT3 at the site of injury in the chronic phase of rats
subjected to either SC-contusion (SCC; moderate or severe) or
SC-transection (SCT; complete or incomplete). The animals were treated
with INDP immediately after injury. Rats subjected to moderate contusion
or incomplete SCT showed significantly higher levels of BDNF and NT-3 as
compared to PBS-immunized ones. In rats with severe SCC and complete
SCT, BDNF and NT-3 concentrations were barely detected. Finally, in the
fourth experiment we assessed motor function recovery in INDP-treated
rats with moderate SC-injury. Rats immunized with A91 showed a
significantly higher motor recovery from the first week and up to 4
months after SC-injury.
Conclusions: The results of this study suggest that PA boosted by
immunization with A91 after moderate SC-injury can exert its benefits
even at chronic stages, as shown by long-term production of BDNF and
NT-3 and a substantial improvement in motor recovery.
Filiaciones:
Univ Anahuac Mexico Norte, Fac Ciencias Salud, Ctr Invest Ciencias Salud CICSA, Huixquilucan, Estado De Mexic, Mexico
Ctr Invest Proyecto CAMINA AC, Mexico City, DF, Mexico
Inst Nacl Psiquiatria Ramon Fuente Muniz, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular & Desarrollo, Mexico City, DF, Mexico
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