Martinez Millan, L. 1, 2 , Zallo, F. . 2 , Pinar, B. . 2 , Gerrikagoitia, I. 2 & Zugaza, J. L. 1, 3
1 Achucarro Basque Center for Neurocscience
2 Department of Neuroscience. Faculty of Medicine. UPV/EHU
3 Department of Genetics, Physical Anthropology and Animal Physiology. Faculty of Science and Technology. UPV/EHU
Changes in the horizontal or vertical component of the natural geomagnetic field leads to expression of c-fos in a variety of brain structures. We have investigated the role of some serin-threonin kinases such as PKCs and MEK1 on the c-fos expression after geomagnetic field application. Using individually, pharmacological inhibitors against PKCs or MEK1, we have observed that c-fos expression decreased significantly compared to the untreated animals. When we pretreated animals simultaneously with both inhibitors, the c-fos expression was dramatically decreased, meaning that PKCs cooperates with MAPkinase pathway to strongly induce this early gene expression.
Similar geomagnetic fields were applied 3 times a day during one week to visually deprived rats as a model of experimental amblyopia. A microarray study of the expression changes of c-fos promoted microRNAs in control visual cortex in comparison with amblyopic cortex revealed a lower expression of microRNAs like Rno-let-7b, Rno-miR-330 and Rno-miR-376c and consequently an increased expression of BDNF, Neurotrophin 3 and Synuclein beta, which are the main targets of these microRNAs. Absence of CpG islands in the promoter regions of the microRNAs mentioned above supress the DNA methylation as a cause of the lower microRNAs expression. In contrast, these changes, probably due to the MAPkinase pathway, were accompanied by an increase of histone acetylation in supragranular visual layers which is considered a parameter of visual recovery.