Blood-Derived α-Synuclein Aggregated in the Substantia Nigra of Parabiotic Mice
Xizhen Ma,
Leilei Chen,
Ning Song,
Le Qu,
Jun Wang,
Junxia Xie
Affiliations
Xizhen Ma
Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China
Leilei Chen
Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China
Ning Song
Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China
Le Qu
Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China
Jun Wang
Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China
Junxia Xie
Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China
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.
