Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD) pathogenesis, and growing evidence has shown that poor sleep quality is one of the risk factors for AD, but the mechanisms of sleep deprivation leading to AD have still not been fully demonstrated. In the present study, we used wild-type (WT) rats to determine the effects of chronic sleep restriction (CSR) on Aβ accumulation. We found that CSR-21d rats had learning and memory functional decline in the Morris water maze (MWM) test. Meanwhile, Aβ42 deposition in the hippocampus and the prefrontal cortex was high after a 21-day sleep restriction. Moreover, compared with the control rats, CSR rats had increased expression of β-site APP-cleaving enzyme 1 (BACE1) and sAPPβ and decreased sAPPα levels in both the hippocampus and the prefrontal cortex, and the BACE1 level was positively correlated with the Aβ42 level. Additionally, in CSR-21d rats, low-density lipoprotein receptor-related protein 1 (LRP-1) levels were low, while receptor of advanced glycation end products (RAGE) levels were high in the hippocampus and the prefrontal cortex, and these transporters were significantly correlated with Aβ42 levels. In addition, CSR-21d rats had decreased plasma Aβ42 levels and soluble LRP1 (sLRP1) levels compared with the control rats. Altogether, this study demonstrated that 21 days of CSR could lead to brain Aβ accumulation in WT rats. The underlying mechanisms may be related to increased Aβ production via upregulation of the BACE1 pathway and disrupted Aβ clearance affecting brain and peripheral Aβ transport.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development. 相似文献
mtDNA COII gene sequences were identified and analyzed using different types of software, namely, MEGA5.0, DNAMAN, and DnaSP5.0 in four Chinese provinces, namely, Sichuan, Zhejiang, Guizhou and Shanghai. Analysis of molecular genetic variation and its genetic structure and differentiation, combined with NJ tree, MP tree analysis and analysis of molecular variance (AMOVA), at Fst = 0.0582 conclude that the genetic differentiation is low, gene flow is Nm = 8.0911, and gene exchange is sufficient. However, for the geographic populations of Pseudoregma bambucicola in the four provinces, their gene exchange is relatively weak at Nm = 0.8284, whereas the genetic differentiation is high at Fst = 0.3764. Based on the data, total nucleotide diversity between the populations is 0.00158 ± 0.00021. The results showed that the total population of Tajima’s D and Fu’s Fs results are D = ?0.885 and Fs = 0.226, respectively. The experimental numerical results showed that this total population is not significant (P > 0.10), indicating that nine different geographic populations are short-term. No expansion occurred in the internal population. This study provided a theoretical and practical basis for the comprehensive prevention and control of P. bambucicola.相似文献
The changes of inheritance mode and fitness of resistance in Helicoverpa armigera (Hübner) along with its resistance evolution to Cry1Ac toxin were evaluated in the laboratory. The resistance levels reached 170.0-, 209.6- and 2893.3-fold, on selection of the field population in the 16th (BtR-F(16)), 34th (BtR-F(34)) and 87th (BtR-F(87)) generation with artificial diet containing Cry1Ac toxin, respectively. As the resistance levels increased, more larvae feeding on the Bt cotton expressing Cry1Ac toxin survived. Most larvae of BtR-F(87) could develop to the 5th instar and about 3% individuals reached the adult stage. The inheritance of Cry1Ac resistance trait at three resistant levels was autosomal and incompletely recessive, but the degree of dominance decreased as the resistance increased. The resistance was primarily monogenic in BtR-F(16) strain, but polygenic as resistance increased. The relative fitness of H. armigera, measured as a ratio of R(0) (the net replacement rate) of resistant strain divided by R(0) of the susceptible strain, decreased with an increase of the resistance levels, with ratios of 0.79, 0.64 and 0.59 in their respective BtR-F(16), BtR-F(34) and BtR-F(87) strains. 相似文献