2026-04-13T18:27:23Zhttps://recercat.cat/oai/request

oai:recercat.cat:10459.1/677812024-12-05T22:27:29Zcom_2072_3622col_2072_479130

00925njm 22002777a 4500 dc Cerveró Cebrià, Clàudia author Blasco Carmona, Alba author Tarabal Mostazo, Olga author Casanovas i Llorens, Anna author Piedrafita Llorens, Lídia author Navarro, Xavier author Esquerda Colell, Josep author Calderó i Pardo, Jordi author 2020-01-09T11:03:28Z 2020-01-09T11:03:28Z 2018 2020-01-09T11:03:31Z 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. This work was supported by grants from the Ministerio de Economía y Competitividad co-financed by FEDER (SAF2015-70801). http://hdl.handle.net/10459.1/67781 spinal muscular atrophy Motoneuron C-boutons Microglia Sigma-1 receptor Motoneuron synaptic afferents Smn2B/- mouse SMNΔ7 mouse Spinal muscular atrophy 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