Benes_2012_Brain.Res.Bull_87_511

Although c-Fos protein is one of the principal molecules in intracellular signaling, c-fos gene disruption is associated with alterations in neuronal functions that do not correspond to its importance in function. The aim of the study was to evaluate the changes of dopaminergic system together with acetylcholinesterase (AChE) in c-fos disruption (KO). KO male mice showed an increase in D(1)-like receptor (279% of WT) and D(2)-like receptor (345% of WT) binding sites in the cortex. On the gene expression level (assessed by real-time PCR), lower quantities of D(1)R-mRNA (0.64) and D(5)R-mRNA (0.6) were found in females when compared to males in the frontal cortex, higher D(2)R-mRNA in the parietal (1.43) and temporal (2.64) cortex and lower AChE-mRNA (0.67). On the contrary, female striatum contained higher level of D(2)R-mRNA (1.62) and AChE-mRNA (1.57) but lower level of D(3)R-mRNA (0.73). Hypothalamic D(1)R-mRNA, D(2)R-mRNA and D(4)R-mRNA were higher in females (1.38, 1.63, and 1.68, respectively). Disruption of c-fos increased selectively D(5)R-mRNA (1.31) in male parietal cortex, D(2)R-mRNA (1.72) in male temporal cortex, and cerebellar D(2)R-mRNA in both males (1.43) and females (1.42), respectively. In females, we found rather decrease in DR-mRNA. Multiple correlations in mRNA quantities (in WT mice) were found, which changed considerably upon c-fos KO. Main interactions in WT were inter-regional, CNS of KO underwent an extensive restructuring comprising intraregional interactions in the frontal cortex, hypothalamus, and cerebellum. These changes in DR (between others) could be considered as one of the adaptive mechanisms in c-fos KO mice.