Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy

摘要

α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. Inthe pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within theautonomic nervous system with no motor features, but mouse models recapitulating PAFwithout motor dysfunction are lacking. Here, we show that in TgM83+/? mice, inoculation ofα-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Synpathology only through the autonomic pathway to both the central nervous system (CNS)and the autonomic innervation of peripheral organs bidirectionally. In parallel, the micedevelop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosisand hyposmia, without motor dysfunction. Thus, we have generated a mouse model ofpure autonomic dysfunction caused by α-Syn pathology. This model may help define themechanistic link between transmission of pathological α-Syn and the cardinal features ofautonomic dysfunction in α-synucleinopathy.