Mapping of Rat Brain Using the Synuclein-1 Monoclonal Antibody Reveals Somatodendritic Expression of a-Synuclein in Populations of Neurons Homologous to those Vulnerable to Lewy Body Formation in Human Synucleopathies

The neuronal protein a-synuclein has been implicated in the pathogenesis of Parkinson disease and other neurodegenerative diseases. Although many studies report that a-synuclein expression is restricted to neuronal presynaptic terminals, this protein aggregates in Lewy bodies in somata that are typically distant from their axon terminals. Few studies have addressed this paradox and there has been no compelling explanation proposed for the apparent discrepancy between the locus of neuronal a-synuclein expression and the loci of Lewy bodies in the majority of Parkinson disease cases. We explored this issue by extensively characterizing the monoclonal antibody Synuclein-1 (Syn-1) and using this highly selective antibody to map the distribution of a-synuclein throughout rat brain and in human substantia nigra (SN). Additionally, a-synuclein expression in rat SN detected by 2 polyclonal antibodies against a-synuclein was compared with that detected by the Syn-1 antibody. In contrast with many previous reports, a-synuclein was detected by Syn-1 in neuronal somata and dendrites in restricted brain regions, as well as more ubiquitously in axons and terminals. The strongest a-synuclein neuronal expression in rat was found in brainstem and cortical regions that are homologous to regions prone to Lewy body formation in humans. The Syn-1 antibody labeled abundant somatodendritic a-synuclein in both rat and human SN, a major locus of Lewy body formation and neurodegeneration in Parkinson disease. By contrast, very few immunoreactive somata in the rat SN were labeled by the 2 polyclonal antibodies. We explore possible explanations for the differences in conflicting reports of patterns of a-synuclein expression in brain, including differences among antibodies.