Fig. 1

Human-like NM production in AAV-hTyr-injected rats. a Schematic representation of the site of AAV-hTyr unilateral stereotaxic injection above the SNpc of the rat brain. b Representative photomicrographs of a 30-μm-thick ipsilateral SNpc section from an AAV-hTyr-injected rat (1 m post-AAV injection) immunostained for TH (red) and hTyr (green). Scale bar, 500 μm. c Left, representative unstained AAV-hTyr-injected rat brain (2 m post-AAV injection) mounted in a cryostat in which ipsilateral SNpc can be detected macroscopically as a brown, darkened area (dashed outline). A hole was made in the contralateral hemisphere as anatomical reference. Right, representative unstained midbrain from a 62-year-old human control subject (Hu) in which the SNpc can be detected macroscopically (bilateral dashed outlines). d Representative NM-sensitive high-resolution T1-weighted magnetic resonance imaging of an AAV-hTyr-injected rat brain at 2 m post-AAV injection (left, ex-vivo) and of a 59-year-old human control brain (Hu, right, in vivo). SNpc can be detected as a unilateral (AAV-hTyr-injected rodent) or bilateral (human) hyperintense area (dashed outlines). e Representative photomicrograph of an unstained 30-μm-thick ipsilateral SNpc section from an AAV-hTyr-injected rat (2 m post-AAV injection) in which NM is shown in brown. Inset, high magnification of a melanized neuron. Scale bars, 100 μm and 12.5 μm (inset). f Representative photomicrographs of Masson-Fontana melanin staining (NM in dark brown) in 5-μm-thick SNpc sections from an AAV-hTyr-injected rat at 2 m post-AAV injection (left) and an 80-year-old human control subject (Hu, right). Scale bars, 25 μm (left) and 12.5 μm (right). g Representative electron micrograph of NM granules in the ipsilateral SNpc of an AAV-hTyr-injected rat at 4 m post-AAV injection (left) and a 75-year-old human control subject (Hu, right). NM pigment is detected as an electron dense matrix. Characteristic associated lipid droplets are indicated with asterisks. Scale bars, 500 nm