PrP 106-126 Altered PrP mRNA Gene Expression in Mouse Microglia BV-2 Cells

Prion diseases are infectious and fatal neurodegenerative diseases.The pathogenic agent is an abnormal prion protein aggregate.Microglial activation in the centre nervous system is a characteristic feature of prion disease.In this study,we examined the effect of PrP 106-126 on PrP mRNA gene expression in Mouse microglia cells BV-2 by real-time quantitative PCR.PrP mRNA expression level was found to be significantly increased after 18 h exposure of BV-2 cells to PrP 106-126,with 3-fold increase after 18 h and 4.5-fold increase after 24 h and BV-2 cells proliferating occurred correspondingly.Our results provide the first in vitro evidence of the increase of PrP mRNA levels in microglial cells exposed to PrP 106-126,and indicate that microglial cells might play a critical role in prion pathogenesis.

SARM1 participates in axonal degeneration and mitochondrial dysfunction in prion disease

Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss,axonal degeneration,and mitochondrial dysfunction.Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1.We found that depletion or dysfunctional mutation of SARM1 protected against NAD+loss,axonal degeneration,and mitochondrial functional disorder induced by the neurotoxic peptide PrP106-126.NAD+supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect.NAD+supplementation in PrP106-126-incubated N2a cells,SARM1 depletion,and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival.Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP^(106-126) are partially dependent on SARM1 NADase activity.This pathway has potential as a therapeutic target in the early stages of prion disease.

Effects of Northern Hemisphere Annular Mode on terrestrial near-surface wind speed over eastern China from 1979 to 2017

Large-scale ocean‒atmosphere circulations(LOACs)have a pronounced effect on the near-surface wind speed(NSWS).In this study,we discussed the contributions of zonal and meridional flows to NSWS changes and identify the possible association between the Northern Hemisphere Annular Mode(NAM)and the NSWS changes over eastern China from 1979 to 2017.Results show that the reduction in NSWS over eastern China was mainly dominated by the weakening of the zonal wind component.NAM has a considerable effect on the NSWS over eastern China.When the NAM exhibits positive phases,the zonal-mean westerly weakens at low-to-mid-latitudes(10°-40°N).Meanwhile,descending flows prevail near 40°N,and ascending flows persist near 65°N in the troposphere.In the lower troposphere,there are northerly anomalies at low-to-mid-latitudes and southerly anomalies at mid-to-high latitudes(40°-70°N).The anomalous meridional flows transport heat from low to high latitudes and weaken the north‒south air temperature gradient.The decreased air temperature gradient over East Asia reduces the pressure gradient near the surface,decreasing NSWS in eastern China.NAM variations could dominate(32.0±15.8)%of the changes in the annual mean NSWS.Nevertheless,the contribution of NAM to the interannual changes of the zonal component in NSWS could reach(45.0±12.9)%.