Correcting Differential Gene Expression Analysis for Cyto-Architectural Alterations in Substantia Nigra of Parkinson's Disease Patients Reveals Known and Potential Novel Disease-Associated Genes and Pathways.

Several studies have analyzed gene expression profiles in the substantia nigra to better understand the pathological mechanisms causing Parkinson's disease (PD). However, the concordance between the identified gene signatures in these individual studies was generally low. This might have been caused by a change in cell type composition as loss of dopaminergic neurons in the substantia nigra pars compacta is a hallmark of PD. Through an extensive meta-analysis of nine previously published microarray studies, we demonstrated that a big proportion of the detected differentially expressed genes was indeed caused by cyto-architectural alterations due to the heterogeneity in the neurodegenerative stage and/or technical artefacts. After correcting for cell composition, we identified a common signature that deregulated the previously unreported ammonium transport, as well as known biological processes such as bioenergetic pathways, response to proteotoxic stress, and immune response. By integrating with protein interaction data, we shortlisted a set of key genes, such as LRRK2, PINK1, PRKN, and FBXO7, known to be related to PD, others with compelling evidence for their role in neurodegeneration, such as GSK3ß, WWOX, and VPC, and novel potential players in the PD pathogenesis. Together, these data show the importance of accounting for cyto-architecture in these analyses and highlight the contribution of multiple cell types and novel processes to PD pathology, providing potential new targets for drug development.

Abuse of androgenic anabolic drugs with "Cycling" induces hepatic steatosis in adult male mice.

BACKGROUND: The importance of the present study comes from the lack of sufficient information about the reversibility of the potential hepatic histopathological alterations which may result from anabolic androgenic drugs abuse by "Cycling" protocol. So, the aim of this study is to explore the negative effects of Deca-Durabolin abuse in hepatic function and structure during an administration cycle. METHODS: For our purpose, study was performed on 40 male adult mices. Animals were divided into five groups of 8 animals each treated weekly by Deca-Durabolin (nandrolone decanoate) at 30 g/kg of BW during one month (GI); during two months (GII); during three months (GIII); during three months followed by six weeks of treatment discontinuation (GIV) and Control (C). Plasma assay of liver enzymes (ALT and AST) and cytohistological examination to determine the histopathological damage properties of the liver were performed. RESULTS: Our results showed that the animals supported very well the administrated substance. Our study showed an increase in plasma levels of liver enzymes (ALT and AST) with the duration of treatment accompanied by important degenerative changes in hepatic tissue with peliosis evolution after two months of treatment. These damages worsen again 6 weeks after stopping treatment and ended by the development of hepatic steatosis with increases hepatic distress. CONCLUSION: These results ported that the use of AAS with "Cycling" may lead to the development of hepatic steatosis before progressing to more serious pathological liver situations in AAS abusers.

Reversible effects of anabolic steroid abuse on cyto-architectures of the heart, kidneys and testis in adult male mice.

The importance of the present study comes from the lack of sufficient information about the reversibility of the histopathological alterations which may result from anabolic androgenic drugs abuse after some times of stop treatment, as it is one of the prior studies which explored the negative effects of Deca-Durabolin abuse in particular on the hearts, kidneys and testis structures. For this aim, study was performed on 40 male adult mices. Animals were divided into five groups of 8 animals each as follows: treated by Deca-Durabolin (nandrolone decanoate) at 30 g/kg of BW, weekly during one month (GI); two months (GII); three months (GIII); three months followed by six weeks of treatment discontinuation (GIV) and Control (C). Cytohistological exam was performed to determine histopathological damage in heart, kidney and testis tissues. Results showed that the treated animals supported very well the administrated substance. The increase in muscle strength and the absence of aggression were the most noticeable traits in longer-term treated groups. In addition, the gains in body and heart weights increase with duration of treatment and even more after stopping treatment. Our study showed important degenerative changes and disorganization of the histological structure of heart, kidney and testis in the animals of GIII. These damages worsen again 6 weeks after stopping treatment in heart and kidney, and repairs incompletely in the testis. In conclusion, these results confirmed that the use of AAS is associated with a lot of deleterious effects on the cardiac, nephritic and gonadic tissues which cannot be reversible.