Cytoplasmic aggregates of dynactin in iPSC-derived tyrosine hydroxylase-positive neurons from a patient with Perry syndrome. (September 2016)

• Record Type: Journal Article
• Authors: Mishima, Takayasu; Ishikawa, Taizo; Imamura, Keiko; Kondo, Takayuki; Koshiba, Yasushi; Takahashi, Ryosuke; Takahashi, Jun; Watanabe, Akihiro; Fujii, Naoki; Tsuboi, Yoshio; Inoue, Haruhisa
• Is Part Of: Parkinsonism & related disorders. Volume 30(2016)
• Page Start: 67
• Page End: 72
• Publication Date: 2016-09
• Subjects: iPSC -- Tyrosine hydroxylase-positive neuron -- Aggregate -- DCTN1 -- Perry syndrome; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2016.06.007
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Background: Perry syndrome is a rare autosomal dominant disorder clinically characterized by parkinsonism with depression/apathy, weight loss, and central hypoventilation. Eight mutations in DCTN1 gene have been reported. A novel disease model is required because the detailed pathogenesis remains unclear. Methods: To develop a novel model, we generated induced pluripotent stem cells (iPSCs) from a Perry syndrome patient with F52L mutation in DCTN1, and describe clinical and neuroimaging investigations. We differentiated iPSCs into tyrosine hydroxylase (TH)-positive neurons. Immunocytochemistry analyses of control and mutant were performed. Results: The patient displayed levodopa responsive parkinsonism. Dopamine transporter single photon emission tomography showed markedly decreased uptake in the striatum, and metaiodobenzylguanidine cardiac scintigraphy also showed decreased uptake. Perry syndrome TH-positive neurons showed dynactin aggregates in cytoplasm. Conclusions: TH-positive neurons from Perry syndrome iPSCs recapitulated an aspect of the disease phenotype of Perry syndrome. Highlights: We describe clinical and neuroimaging investigations of a Perry syndrome patient. We generate induced pluripotent stem cells (iPSCs) from a Perry syndrome patient. Perry syndrome tyrosine hydroxylase-positive neurons show dynactin aggregates in cytoplasm.