期刊
NEUROBIOLOGY OF DISEASE
卷 51, 期 -, 页码 192-201出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2012.11.010
关键词
Lactadherin; MFGE8; Dopaminergic neurons; Phagocytosis; Neurodegenerative disease; MPTP
资金
- Institut National de la Sante et de la Recherche Medicate
- program Investissements d'avenir [ANR-10-IAIHU-06]
Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by a loss of dopaminergic neurons (DN) in the substantia nigra (SN). Several lines of evidence suggest that apoptotic cell death of DN is driven in part by non-cell autonomous mechanisms implicating microglial cells and inflammatory processes. Yet, how apoptotic DNs get removed by professional phagocytes and how this process modulates inflammatory processes are still unresolved issues. In this study, we investigated the role of MFGE8, a soluble factor involved in phagocytic recognition, in apoptotic DN clearance and neuroinflammation in PD. We report that glial expression of MFGE8 is enhanced in post-mortem PD brains compared to control individuals. Then, in vivo functional analysis of Mfge8 was assessed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD using wild-type (WT) and Mfge8-deficient mice. Neuropathological analysis consisted in evaluating (i) the loss of nigral DN and striatal DN terminals, (ii) the extent of glial cell activation and (iii) the number of apoptotic profiles. In vivo microglial phagocytic activity was further assessed by measuring the engulfment of apoptotic DN preloaded with fluorescent latex beads. Here we show that Mfge8 deficiency neither impact the phagocytic clearance of apoptotic bodies nor change the overall neuropathological parameters (DN cell loss and glial cell activation). In summary, our data argue that MFGE8 is not likely involved in the phagocytic clearance of neuronal debris associated with nigrostriatal pathway injury. (C) 2012 Elsevier Inc. All rights reserved.
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