Cell and Tissue Journal

Abstract Aim: The aim of this study was to compare the gene expression changes and their effects on protein networks, transcription factors prediction, cellular pathways and small RNAs in the transgenic mouse models of Alzheimer’s disease (Tau and Amyloid beta).
Material and Methods: The results of the brain tissue microarray data from two models of Alzheimer’s disease were analyzed in GEO database. Protein networks prediction performed using String database and analyzed by Cytoscape software. The changed genes were used for prediction of transcription factors (TFs) and cellular pathways via Enrichr web service. Moreover, the ToppGene portal was used for prediction of the role of small RNAs involved in these models.
Results:Analysis of protein networks have showed that the CTSS gene (encode Cathepsin S), a lysosomal cysteine protease, was the key gene and the main inter-network linker in the both models. Also, the data from evaluation of TFs resulting to introduce of IRF8 genes (encode Interferon Regulatory Factor 8) and NFE2L2 (encode Nuclear Factor, Erythroid 2 Like 2) that are involved in the immune system and oxidative stress respectively. On the other hand, we have shown that let-7 small RNA, which is involved in the immune system, could act as a major regulator in these gene pathways.
Conclusions: The immune system has a critical role in the both models of Alzheimer’s disease and seems that the control of the immune-related genes (IRF8 and let-7) activity besides decrease of oxidative stress (CTSS and NFE2L2) in both models is a plausible therapeutic target.
 

Abstract Aim: The aim of this study was to investigate of cuprizone time-dependent effects on MAG, MOG, MBP, and PLP proteins and demyelination process.
Materials and Methods: The myelin degradation model was created with a five week diet containing 0.2% of cuprizone. The rats brain corpus callosum region was subjected to tissue and molecular evaluation at weeks 3, 4 and 5. At the end of the fifth week, behavioral studies were performed by open field test.
Results: Results showed that the expression of myelin sheath proteins decreased time-dependently in comparison with the control group. Despite the overall reduction of these proteins in the third week, only PLP protein decreased significantly in this week comparing to control (p < /em><0.01). Other proteins also showed a significant reduction in expression after the fourth week. Electron microscopy studies showed significant changes in the reduction of myelin diameter in comparison to the control group only after 4 weeks (p < 0.01). Behavioral studies also indicated that cuprizone was able to cause significant behavioral abnormalities in the animals from the beginning of the third week compared to the control group.
Conclusion: This research was the first time to study the main myelin proteins at the same time, and the results show that the best time for accurate molecular, tissue and behavioral reviews are fourth and fifth weeks.