Caudo‐rostral brain spreading of α‐synuclein through vagal connections

SNc (Substantia nigra, compact part) UBERON:0001965 projects to MY (Medulla) UBERON:0001896 · Rat

Despite widespread rostral appearance of the medulla-derived human alpha-synuclein, no labelling was found in the substantia nigra pars compacta and dopaminergic cell numbers were unchanged; the authors attribute this to the lack of a direct anatomical link between the SNc and the medulla.

Results (SNc paragraph); Discussion

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HY (Hypothalamus) UBERON:0001898 projects to MY (Medulla) UBERON:0001896 · Rat

At 18 weeks, forebrain sections showed human alpha-synuclein-immunoreactive axonal projections in the hypothalamus after the protein had been expressed only in medullary neurons, interpreted as spread along hypothalamic fibres that reach the medulla.

Fig 2E,I

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PAG (Periaqueductal gray) UBERON:0003040 projects to MY (Medulla) UBERON:0001896 · Rat

Axonal profiles stained for human alpha-synuclein appeared in the periaqueductal gray of high-expressor rats 18 weeks after the protein had been expressed exclusively in medullary neurons, indicating transfer along fibres linking the periaqueductal gray with the medulla.

Fig 2E,G

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PP (Peripeduncular nucleus) UBERON:0002144 projects to MY (Medulla) UBERON:0001896 · Rat

Human alpha-synuclein-labelled axons were seen in the region of the peripeduncular nucleus, dorsolateral to substantia nigra pars reticulata, at 18 weeks after medullary expression of the protein.

Fig 2E,H

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LC (Locus ceruleus) UBERON:0002148 projects to MY (Medulla) UBERON:0001896 · Rat

Human alpha-synuclein expressed only in medullary neurons was later found in axonal fibres within the pontine coeruleus–subcoeruleus complex, some of which were also tyrosine hydroxylase positive, taken as evidence of protein transfer along the direct projection these cells send to the medulla.

Fig 2E,F; Supporting Information Fig S3

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P (Pons) UBERON:0000988 projects to MY (Medulla) UBERON:0001896 · Rat

After AAV-driven overexpression of human alpha-synuclein restricted to medullary neurons (vagus nerve injection), immunoreactive axons appeared in the pons by 8 weeks and increased markedly by 18 weeks, both ipsilateral and, at roughly a third of the ipsilateral count, contralateral to the injection; the authors attribute this to transfer of the protein into fibres of pontine neurons that innervate the medulla.

Fig 2A–D, Results (spreading section)

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AMY (amygdala) UBERON:0001876 projects to MY (Medulla) UBERON:0001896 · Rat

The amygdala in the medial temporal lobe was listed among the predilection sites containing human alpha-synuclein-labelled neurites at 18 weeks after vagal vector injection, attributed to its direct fibre connection with the medulla.

Fig 2E; Results (topographical distribution)

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DR (Dorsal nucleus raphe) UBERON:0002043 projects to MY (Medulla) UBERON:0001896 · Rat

Fibres immunoreactive for the medulla-derived human alpha-synuclein were detected in the dorsal raphe at 18 weeks after vagal vector injection, consistent with spread through axons connecting this nucleus with the medulla.

Fig 2E; Results (topographical distribution)

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