CCAAT/Enhancer binding protein β silencing mitigates glial activation and neurodegeneration in a rat model of Parkinson’s disease

The CCAAT/Enhancer binding protein β (C/EBPβ) is a transcription factor involved in numerous physiological as well as pathological conditions in the brain. However, little is known regarding its possible role in neurodegenerative disorders. We have previously shown that C/EBPβ regulates the expression of genes involved in inflammatory processes and brain injury. Here, we have analyzed the effects of C/EBPβ interference in dopaminergic cell death and glial activation in the 6-hydroxydopamine model of Parkinson’s disease. Our results showed that lentivirus-mediated C/EBPβ deprivation conferred marked in vitro and in vivo neuroprotection of dopaminergic cells concomitant with a significant attenuation of the level of the inflammatory response and glial activation. Additionally, C/EBPβ interference diminished the induction of α-synuclein in the substantia nigra pars compacta of animals injected with 6-hydroxydopamine. Taking together, these results reveal an essential function for C/EBPβ in the pathways leading to inflammatory-mediated brain damage and suggest novel roles for C/EBPβ in neurodegenerative diseases, specifically in Parkinson’s disease, opening the door for new therapeutic interventions.This work was supported by MINECO (Grants SAF2010-16365 and SAF2014-52940-R to A.P-C) and MINECO (SAF-2012-34556 to J.G-C), and partially financed with FEDER funds. CIBERNED is funded by the Instituto de Salud Carlos III. J.A.M-G. is a post-doctoral fellow from CIBERNED.Peer reviewe