dc.contributor.author |
Cerveró Cebrià, Clàudia |
dc.contributor.author |
Blasco Carmona, Alba |
dc.contributor.author |
Tarabal Mostazo, Olga |
dc.contributor.author |
Casanovas i Llorens, Anna |
dc.contributor.author |
Piedrafita Llorens, Lídia |
dc.contributor.author |
Navarro, X. (Xavier) |
dc.contributor.author |
Esquerda Colell, Josep |
dc.contributor.author |
Calderó i Pardo, Jordi |
dc.date |
2020-01-09T11:03:28Z |
dc.date |
2020-01-09T11:03:28Z |
dc.date |
2018 |
dc.date |
2020-01-09T11:03:31Z |
dc.identifier |
0022-3069 |
dc.identifier |
http://hdl.handle.net/10459.1/67781 |
dc.identifier |
https://doi.org/10.1093/jnen/nly033 |
dc.identifier.uri |
http://hdl.handle.net/10459.1/67781 |
dc.description |
Spinal muscular atrophy (SMA) is characterized by the loss of α-motoneurons (MNs) with concomitant muscle denervation. MN excitability and vulnerability to disease are particularly regulated by cholinergic synaptic afferents (C-boutons), in which Sigma-1 receptor (Sig1R) is concentrated. Alterations in Sig1R have been associated with MN degeneration. Here, we investigated whether a chronic treatment with the Sig1R agonist PRE-084 was able to exert beneficial effects on SMA. We used a model of intermediate SMA, the Smn2B/− mouse, in which we performed a detailed characterization of the histopathological changes that occur throughout the disease. We report that Smn2B/− mice exhibited qualitative differences in major alterations found in mouse models of severe SMA: Smn2B/− animals showed more prominent MN degeneration, early motor axon alterations, marked changes in sensory neurons, and later MN deafferentation that correlated with conspicuous reactive gliosis and altered neuroinflammatory M1/M2 microglial balance. PRE-084 attenuated reactive gliosis, mitigated M1/M2 imbalance, and prevented MN deafferentation in Smn2B/− mice. These effects were also observed in a severe SMA model, the SMNΔ7 mouse. However, the prevention of gliosis and MN deafferentation promoted by PRE-084 were not accompanied by any improvements in clinical outcome or other major pathological changes found in SMA mice. |
dc.description |
This work was supported by grants from the Ministerio de Economía y Competitividad co-financed by FEDER (SAF2015-70801). |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
American Association of Neuropathologists |
dc.relation |
MINECO/PN2013-2016/SAF2015–70801 |
dc.relation |
Versió postprint del document publicat a: https://doi.org/10.1093/jnen/nly033 |
dc.relation |
Journal of Neuropathology and Experimental Neurology, 2018, vol. 77, num. 7, p. 577-597 |
dc.rights |
(c) American Association of Neuropathologists, 2018 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
spinal muscular atrophy |
dc.subject |
Motoneuron |
dc.subject |
C-boutons |
dc.subject |
Microglia |
dc.subject |
Sigma-1 receptor |
dc.subject |
Motoneuron synaptic afferents |
dc.subject |
Smn2B/- mouse |
dc.subject |
SMNΔ7 mouse |
dc.subject |
Spinal muscular atrophy |
dc.title |
Glial activation and central synapse loss, but not motoneuron degeneration, are prevented by the sigma-1 receptor agonist PRE-084 in the Smn2B/- mouse model of spinal muscular atrophy |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/acceptedVersion |