Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

ADS Injector-I 2 K superfluid helium cryogenic system

The Accelerator Driven Sub-critical(ADS)system is a strategic plan to solve the nuclear waste problem for nuclear power plants in China.High-energy particle accelerators and colliders contain long strings of superconducting devices,superconducting radio frequency cavities,and magnets,which may require cooling by 2 K superfluid helium(HeliumⅡ).2 K superfluid helium cryogenic system has become a research hot spot in the field of superconducting accelerators.In this study,the ADS Injector-I 2 K cryogenic system is examined in detail.The cryogenic system scheme design,key equipment,and technology design,such as the 2 K Joule–Thomson(J–T)heat exchanger and cryomodules CM1+CM2 design,are examined,in addition to the commissioning and operation of the cryogenic system.The ADS Injector-I 2 K cryogenic system is the first 100 W superfluid helium system designed and built independently in China.The ADS proton beam reached 10 Me V at 10 m A in July 2016 and 10 Me V at 2 m A in continuous mode in January 2017 and has been operated reliably for over 15,000 h,proving that the design of ADS Injector-I 2 K cryogenic system,the key equipment,and technology research are reasonable,reliable,and meet the requirements.The research into key technologies provides valuable engineering experience that can be helpful for future projects such as CI-ADS(China Initiative Accelerator-Driven System),SHINE(Shanghai High Repetition Rate XFEL and Extreme Light Facility),PAPS(Platform of Advanced Photon Source Technology),and CEPC(Circular Electron-Positron Collider),thereby developing national expertise in the field of superfluid helium cryogenic systems.

Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson’s disease

Autophagy has been shown to play an important role in Parkinson’s disease.We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson’s disease through affecting autophagy.In this study,6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells(SKP-SCs).The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine,reduced excessive autophagy,increased tyrosine hydroxylase expression,reducedα-synuclein expression,reduced the autophagosome number,and activated the PI3K/AKT/mTOR pathway.Autophagy activator rapamycin inhibited the effects of SKP-SCs,and autophagy inhibitor 3-methyladenine had the opposite effect.These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy,thereby exhibiting a neuroprotective effect in a cellular model of Parkinson’s disease.This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University(approval No.S20181009-205)on October 9,2018.