| First Author | Ferro A | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 7 | Pages | e0200013 |
| PubMed ID | 29975753 | Mgi Jnum | J:263838 |
| Mgi Id | MGI:6189248 | Doi | 10.1371/journal.pone.0200013 |
| Citation | Ferro A, et al. (2018) Inhibition of NF-kappaB signaling in IKKbetaF/F;LysM Cre mice causes motor deficits but does not alter pathogenesis of Spinocerebellar ataxia type 1. PLoS One 13(7):e0200013 |
| abstractText | Spinocerebellar Ataxia type 1 (SCA1) is a fatal neurodegenerative genetic disease that is characterized by pronounced neuronal loss and gliosis in the cerebellum. We have previously demonstrated microglial activation, measured as an increase in microglial density in cerebellar cortex and an increase in the production of pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), in the cerebellum of the ATXN1[82Q] transgenic mouse model of SCA1. To examine the role of activated state of microglia in SCA1, we used a Cre-Lox approach with IKKbetaF/F;LysM Cre mice intended to reduce inflammatory NF-kappaB signaling, selectively in microglia. ATXN1[82Q];IKKbetaF/F;LysM Cre mice showed reduced cerebellar microglial density and production of TNFalpha compared to ATXN1[82Q] mice, yet reducing NF-kappaB did not ameliorate motor impairments and cerebellar cellular pathologies. Unexpectedly, at 12 weeks of age, control IKKbetaF/F;LysM Cre mice showed motor deficits equal to ATXN1[82Q] mice that were dissociated from any obvious neurodegenerative changes in the cerebellum, but were rather associated with a developmental impairment that presented as a retention of climbing fiber synaptic terminals on the soma of Purkinje neurons. These results indicate that NF-kappaB signaling is required for increase in microglial numbers and TNF-alpha production in the cerebella of ATXN1[82Q] mouse model of SCA1. Furthermore, these results elucidate a novel role of canonical NF-kappaB signaling in pruning of surplus synapses on Purkinje neurons in the cerebellum during development. |
