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Research Database PMU-SQQUID

Striatal transplantation for multiple system atrophy - Are grafts affected by alpha-synucleinopathy?
Stefanova, N; Hainzer, M; Stemberger, S; Couillard-Despres, S; Aigner, L; Poewe, W; Wenning, GK
EXP NEUROL. 2009; 219(1): 368-371.
Originalarbeiten (Zeitschrift)

PMU-Authors

Aigner Ludwig
Couillard-Despr├ęs S├ębastien

Abstract

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
Striatonigral degeneration
alpha-synuclein
Glial cytoplasmic inclusions
Transgenic mouse
Striatal transplantation