Immunolocalization of human alpha-synuclein in the Thy1-aSyn ("Line 61") transgenic mouse line

Alpha-synuclein (a-syn) is the major component of the intracytoplasmic inclusions known as Lewy bodies (LB), which constitute the hallmark of Parkinson's disease (PD). Mice overexpressing human a-syn under the Thy-1 promoter (ASO) show slow neurodegeneration and some behavioral deficits similar to those seen in human PD patients. Here, we describe a whole-brain distribution of human a-syn in adult ASO mice. We find that the human a-syn is ubiquitously distributed in the brain including the cerebellar cortex, but the intensity and sub-cellular localization of the staining differed in the various regions of the central nervous system. Among particular CNS areas with human a-syn immunoreactivity, we describe staining patterns in the olfactory bulb, cortex, hippocampus, thalamic region, brainstem nuclei and cerebellar cortex. This immunohistochemical study provides an anatomical map of the human a-syn distribution in ASO mice. Our data show that human a-syn, although not present at levels that were detectable by immunostaining in dopaminergic neurons of substantia nigra or noradrenergic neurons of locus coeruleus, was highly expressed in other PD relevant regions of the brain in different neuronal subtypes. These data will help to relate a-syn expression to the phenotypic manifestations observed in this widely used mouse line.