Transient transfection of human CDNF gene reduces the 6-hydroxydopamine-induced neuroinflammation in the rat substantia nigra

Show full item record



Permalink

http://hdl.handle.net/10138/162223

Citation

Nadella , R , Voutilainen , M H , Saarma , M , Gonzalez-Barrios , J A , Leon-Chavez , B A , Dueas Jimnez , J M , Dueas Jimnez , S H , Escobedo , L & Martinez-Fong , D 2014 , ' Transient transfection of human CDNF gene reduces the 6-hydroxydopamine-induced neuroinflammation in the rat substantia nigra ' , Journal of Neuroinflammation , vol. 11 , 209 . https://doi.org/10.1186/s12974-014-0209-0

Title: Transient transfection of human CDNF gene reduces the 6-hydroxydopamine-induced neuroinflammation in the rat substantia nigra
Author: Nadella, Rasajna; Voutilainen, Merja H.; Saarma, Mart; Gonzalez-Barrios, Juan A.; Leon-Chavez, Bertha A.; Dueas Jimnez, Judith M.; Dueas Jimnez, Sergio H.; Escobedo, Lourdes; Martinez-Fong, Daniel
Contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2014-12-16
Language: eng
Number of pages: 18
Belongs to series: Journal of Neuroinflammation
ISSN: 1742-2094
URI: http://hdl.handle.net/10138/162223
Abstract: BACKGROUND: The anti-inflammatory effect of the cerebral dopamine neurotrophic factor (CDNF) was shown recently in primary glial cell cultures, yet such effect remains unknown both in vivo and in 6-hydroxydopamine (6-OHDA) models of Parkinson's disease (PD). We addressed this issue by performing an intranigral transfection of the human CDNF (hCDNF) gene in the critical period of inflammation after a single intrastriatal 6-OHDA injection in the rat. METHODS: At day 15 after lesion, the plasmids p3xNBRE-hCDNF or p3xNBRE-EGFP, coding for enhanced green florescent protein (EGFP), were transfected into the rat substantia nigra (SN) using neurotensin (NTS)-polyplex. At day 15 post-transfection, we measured nitrite and lipoperoxide levels in the SN. We used ELISA to quantify the levels of TNF-α, IL-1β, IL-6, endogenous rat CDNF (rCDNF) and hCDNF. We also used qRT-PCR to measure rCDNF and hCDNF transcripts, and immunofluorescence assays to evaluate iNOS, CDNF and glial cells (microglia, astrocytes and Neuron/Glial type 2 (NG2) cells). Intact SNs were additional controls. RESULTS: In the SN, 6-OHDA triggered nitrosative stress, increased inflammatory cytokines levels, and activated the multipotent progenitor NG2 cells, which convert into astrocytes to produce rCDNF. In comparison with the hemiparkinsonian rats that were transfected with the EGFP gene or without transfection, 6-OHDA treatment and p3xNBRE-hCDNF transfection increased the conversion of NG2 cells into astrocytes resulting in 4-fold increase in the rCDNF protein levels. The overexpressed CDNF reduced nitrosative stress, glial markers and IL-6 levels in the SN, but not TNF-α and IL-1β levels. CONCLUSION: Our results show the anti-inflammatory effect of CDNF in a 6-OHDA rat of Parkinson's disease. Our results also suggest the possible participation of TNF-α, IL-1β and IL-6 in rCDNF production by astrocytes, supporting their anti-inflammatory role.
Subject: NG2 cells
Astrocytes
NBRE promoter
Neurotrophic factor
CDNF
Polyplex
Cytokines
Nitrosative stress
TUMOR-NECROSIS-FACTOR
MIDBRAIN DOPAMINE NEURONS
AFFINITY NEUROTENSIN RECEPTOR
NEUROTROPHIC FACTOR CDNF
PARKINSONS-DISEASE
FACTOR-ALPHA
TNF-ALPHA
IN-VIVO
NG2 CELLS
ANTIINFLAMMATORY CYTOKINE
1182 Biochemistry, cell and molecular biology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
12974_2014_Article_209.pdf 3.273Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record