Striatal transplantation for multiple system atrophy--are grafts affected by alpha-synucleinopathy?

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 re-innervation 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.

• Authors: Nadia Stefanova, Monika Hainzer, Sylvia Stemberger, Sebastien Couillard-Després, Ludwig Aigner, Werner Poewe, Gregor K Wenning
• Journal: Experimental neurology (Exp Neurol) Vol. 219 Issue 1 Pg. 368-71 (Sep 2009) ISSN: 1090-2430 [Electronic] United States
• PMID: 19460374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Synuclein
• Dopamine

Topics

• Animals
• Brain Tissue Transplantation (methods)
• Corpus Striatum (metabolism, physiopathology, transplantation)
• Disease Models, Animal
• Dopamine (physiology)
• Encephalitis (etiology, pathology, physiopathology)
• Gliosis (etiology, pathology, physiopathology)
• Graft Survival (physiology)
• Growth Cones (metabolism)
• Humans
• Inclusion Bodies (metabolism, pathology)
• Mice
• Mice, Transgenic
• Multiple System Atrophy (metabolism, physiopathology, surgery)
• Oligodendroglia (metabolism, pathology)
• Stem Cell Transplantation (methods)
• Substantia Nigra (metabolism)
• Treatment Outcome
• alpha-Synuclein (metabolism)