PMU-Autor/inn/en
Aigner LudwigAbstract
Multiple system atrophy (MSA), a fatal neurodegenerative disorder, is the second most common cause of parkinsonism and frequently associated with autonomic failure. Previous work from our laboratory has shown that striatal grafts survive and exert functional effects in toxin-induced rodent models of MSA-P, the parkinson variant characterized by levodopa resistance due to loss of striatal medium-sized spiny neurons. It is unknown whether oligodendroglial alpha-synuclein signature lesions affect graft survival in MSA. Recent reports on neurotransplantation in Parkinson's disease patients suggest a possible host-to-graft disease propagation of alpha-synuclein pathology which may be relevant to transplantation in MSA as well. We here demonstrate that embryonic E14 striatal allografts show reduced p-zone volume and dopaminergic graft reinnervation accompanied by increased gliosis in a transgenic MSA mouse model featuring alpha-synuclein oligodendrogliopathy. Oligodendrocytes expressing host-specific alpha-synuclein migrate into the graft tissue after 3 months of survival. Our data suggest that the presence of MSA-like alpha-synuclein oligodendrogliopathy and related to it pro-inflammatory microenvironment may compromise the connectivity and neurorestorative outcome of striatal grafts. (C) 2009 Elsevier Inc. All rights reserved.
Useful keywords (using NLM MeSH Indexing)
Animals
Brain Tissue Transplantation/methods*
Corpus Striatum/metabolism
Corpus Striatum/physiopathology
Corpus Striatum/transplantation*
Disease Models, Animal
Dopamine/physiology
Encephalitis/etiology
Encephalitis/pathology
Encephalitis/physiopathology
Gliosis/etiology
Gliosis/pathology
Gliosis/physiopathology
Graft Survival/physiology*
Growth Cones/metabolism
Humans
Inclusion Bodies/metabolism
Inclusion Bodies/pathology
Mice
Mice, Transgenic
Multiple System Atrophy/metabolism
Multiple System Atrophy/physiopathology
Multiple System Atrophy/surgery*
Oligodendroglia/metabolism
Oligodendroglia/pathology
Stem Cell Transplantation/methods*
Substantia Nigra/metabolism
Treatment Outcome
alpha-Synuclein/metabolism*
Find related publications in this database (Keywords)
Multiple system atrophy