Abstract
As a pathological biomarker of Parkinson’s disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the brains of mice and whether α-synuclein in the brain could be cleared by parabiosis. Heterochronic parabiosis was performed on SNCAA53T transgenic mice (A53T mice) and wildtype mice. The levels of human α-synuclein in the blood and substantia nigra of wildtype mice were significantly increased after 4-month parabiosis with A53T mice. Moreover, the expression of α-synuclein filament, but not of total α-synuclein, was significantly increased in the substantia nigra of wildtype mice that were paired with A53T mice. However, the levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system; however, it appears to be difficult to clear it from the brain in a short period of time.
Highlights
IntroductionThe levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice
No dopaminergic neuron loss in substantia nigra of A53T mice was found until 10 months old [20], which is consistent with our result
In order to avoid the interference caused by Hu-α-syn generation after the age of 6 months, parabiosis surgery was performed on the 2-month-old mice, and the time period of parabiosis was set to 4 months
Summary
The levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system; it appears to be difficult to clear it from the brain in a short period of time. That study did not determine whether pathological αsynuclein can continuously exist in the central nervous system, as it is limited by low levels of α-synuclein. As there are seven amino acids that differ between mouse α-synuclein and Hu-α-syn [17], specific antibodies were constructed and ELISA was employed to identify the level of Hu-α-syn
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