Attenuation of MPTP/MPP(+) toxicity in vivo and in vitro by an 18-mer peptide derived from prosaposin.

Parkinson's disease (PD) is a chronic progressive neurological disorder with an increasing incidence in the aging population. Neuroprotective and/or neuroregenerative strategies remain critical in the treatment of this increasingly prevalent disease. Prosaposin is a neurotrophic factor whose neurotrophic activity is attributed to a stretch of 12 amino acids located at the N-terminal region of saposin C. The present study was performed to investigate the protective effect and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) in Parkinson's disease models. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium ion (MPP(+))-induced dopaminergic neurotoxicity in C57BL/6J mice or SH-SY5Y cells and explored the protective effect and mechanisms of action of PS18 on dopaminergic neurons. Treatment with 2.0mg/kg PS18 significantly improved behavioral deficits, enhanced the survival of tyrosine hydroxylase-positive neurons, and decreased the activity of astrocytes in the substantia nigra and striatum in MPTP-induced PD model mice. In vitro, a Cell Counting Kit-8 assay and Hoechst 33258 staining revealed that co-treatment with 300ng/mL PS18 and 5mM MPP(+) protected against MPP(+)-induced nuclear morphological changes and attenuated cell death induced by MPP(+). We also found that PS18-FAM entered the cells, and the retention time of PS18-FAM in the cytoplasm of MPP(+)-treated cells was shorter than that of untreated cells. In addition, PS18 showed protection from MPP(+)/MPTP-induced apoptosis in the SH-SY5Y cells and dopaminergic neurons in the PD model mice via suppression of the c-Jun N-terminal kinase/c-Jun pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases such as PD.

A double aortic arch with a deformed trachea accompanied by a subaortic left innominate vein.

During our dissection of a Japanese elderly female cadaver, a double aortic arch with a deformed trachea was found in the cadaver. The ascending aorta was bifurcated to form the left (anterior) and right (posterior) aortic arches. Encircling and compressing the trachea and esophagus, they confluenced into the descending aorta. We concluded that it was a case of the double aortic arch forming a vascular ring. In the vascular ring the trachea was deformed. In addition, the left innominate vein coursed under the aortic arches (subaortic left innominate vein, SLIV) and crossed the mediastinum posterior to the ascending aorta and anterior to the trachea.