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The tau and TDP-43 pathologies differed from psyn pathology in both shape and localization; most psyn pathologies were not colocalized with ptau-positive structures and the overlap was small.
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The distribution of psyn pathology is illustrated in Figure 8D.
Induction and propagation of psyn pathology were examined by IHC.
Psyn pathology was mainly observed in neurites and perinuclear regions.
Psyn pathology was accumulated mainly in neurites, and partly in soma.
In the case of injection into Str, psyn pathology was observed in amygdala, SN and a wide range of cortices.
These findings strongly indicate that spreading of psyn pathology does not occur by simple diffusion or nonspecific transport.
Pretreatment of brain sections with formic acid and heat enabled detection of psyn pathology at only 1 month after injection.
This strongly suggests that propagation of psyn pathology induced motor phenotypes, although we could not detect cognitive dysfunction in the Y-maze test.
Injection of αsyn fibrils into EC induced severe psyn pathology in EC (3.52 mm posterior to bregma), dentate gyrus (3.52 mm posterior to bregma), hippocampal CA3 region (1.94 and 3.52 mm posterior to bregma), fimbria (1.94 mm posterior to bregma), and septal nuclei (0.02 mm anterior to bregma) on the injection side, as well as moderate psyn pathology in hippocampus on the contralateral side.
When αsyn fibrils were injected into SN, psyn pathology only appeared in the central nucleus of amygdala and stria terminalis, which are located far from SN, while there was no detectable psyn pathology around SN. Amygdala is connected with SN [ 30], and stria terminalis serves as a major output pathway of the central nucleus of amygdala.
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