Abstract
Context: Safranal (SAF) is verified to have potential effects in promoting nerve growth.Objectives: This study verifies the role of SAF in promoting dopaminergic neurons growth in vitro and in vivo.Material and methods: Rat neural stem cells (NSC) were treated with 1, 20, or 100 ng/mL of SAF, and the expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) were assayed by flow cytometry and real-time PCR and the secretion of dopamine (DA) was assayed by ELISA. Then, 2 × 106 cells of SAF-treated NSC was administrated into PD rat models induced by 6-OHDA. The differentiation and survival of dopaminergic neurons was identified by fluorescence microscope and TH+ cells by immunostaining and DA secretion by ELISA at week 2 and week 4, respectively.Results: After being treated with SAF at 20 and 100 ng/mL for 1 week, TH and DAT positive rates increased 1.4- and 1.7-fold (p < 0.01, respectively). TH and DAT mRNA also increased 8.05- and 4.41-fold, respectively. And the release of DA statistically increased 1.5-fold (p < 0.01). In vivo, the number of rotations decreased to 4.33 ± 0.97 rpm (p < 0.01) and the survival rates increased to 77.66 ± 7.87% (p < 0.05) at week 4 after transplantation of SAF-treated NSC. Moreover, the transplanted cells increased three-fold, TH fluorescence density increased four-fold and DA releases increased 1.4-fold (p < 0.01) at week 4 after transplantation.Conclusions: SAF promoted the production of functional DA cells and alleviated PD, which may contribute to a new therapy for PD patients.
Highlights
Parkinson’s disease (PD) is a chronic neurodegenerative disease occurring in middle-aged and senior people, characterized by slow progress of dopamine (DA) neuron degeneration and death in the midbrain substantia nigra pars compacta (SNc) resulting in the loss of DA nerve endings in the striatum, causing tremors, muscle rigidity, bradykinesia, postural instability, and a series of syndromes (Farzanehfar 2016)
The number of rotations decreased to 4.33 ± 0.97 rpm (p < 0.01) and the survival rates increased to 77.66 ± 7.87% (p < 0.05) at week 4 after transplantation of SAF-treated neural stem cells (NSC)
SAF promoted the production of functional DA cells and alleviated PD, which may contribute to a new therapy for PD patients
Summary
Parkinson’s disease (PD) is a chronic neurodegenerative disease occurring in middle-aged and senior people, characterized by slow progress of dopamine (DA) neuron degeneration and death in the midbrain substantia nigra pars compacta (SNc) resulting in the loss of DA nerve endings in the striatum, causing tremors, muscle rigidity, bradykinesia, postural instability, and a series of syndromes (Farzanehfar 2016). A potential therapeutic approach to PD which has been developed for the last decade is the implantation of DA-producing cells into the striatum, which replaces part of the lost DA neurons function, and secretes neurotrophic factors to inhibit the loss of DA neurons. Stem cells are potentially carcinogenic and this is an invasive treatment. It is not a reliable widespread therapy to use
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