title: Testosterone-induced persistent susceptibility to Plasmodium chabaudi malaria: long-term changes of lincRNA and mRNA expression in the spleen.
abstract: Testosterone (T) is known to induce persistent susceptibility to blood-stage malaria of Plasmodium chabaudi in otherwise resistant female C57BL/6 mice, which is associated with permanent changes in mRNA expression of the liver. Here, we investigate the spleen as the major effector against blood-stage malaria for any possible T-induced long-term effects on lincRNA and mRNA expression. Female C57BL/6 mice were treated with T for 3 weeks, then T was withdrawn for 12 weeks before challenging with P. chabaudi. LincRNA and mRNA expression was examined after 12 weeks of T-withdrawal and after subsequent infections using Agilent whole mouse genome oligo microarrays. Our data show for the first time long-term effects of T on lincRNA expression evidenced directly as persistent changes after T-withdrawal for 12 weeks and indirectly as altered responsiveness of expression to P. chabaudi infections. There are 3 lincRNA-species upregulated and 10 lincRNAs downregulated by more than 2-fold (p<0.01). In addition, 11 and 10 mRNAs are persistently up- and downregulated by T, respectively. These changes remain not sustained during infections at peak parasitemia, when 15 other lincRNAs and 9 other mRNAs exhibit an altered expression. The only exception is the Tnk1-mRNA encoding the non-receptor tyrosine kinase 1 that is persistently downregulated by 0.34-fold after T-withdrawal and that becomes upregulated by 5.9-fold upon infection at peak parasitemia, suggesting an involvement of tyrosine phosphorylation by Tnk1 in mediating long-term effects of T in the spleen. The T-induced changes in splenic mRNA expression are totally different to those previously observed in the liver. Collectively, our data support the view that T induces long-term organ-specific changes in both lincRNA and mRNA expression, that presumably contribute to organ-specific dysfunctions upon infection with blood-stage malaria of P. chabaudi.
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia. mohameddkhil@yahoo.com
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Dkhil
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Quraishy
authors.forename: Denis
authors.initials: D
authors.lastname: Delic
authors.forename: Abdel-Azeem
authors.initials: AA
authors.lastname: Abdel-Baki
authors.forename: Frank
authors.initials: F
authors.lastname: Wunderlich
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004198:Disease Susceptibility; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008288:Malaria / Q000235:genetics* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000187:drug effects*; D025341:Principal Component Analysis; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D013739:Testosterone