Manipulation of CREB related gene expression in neurons influences adult neurogenesis and morris water maze strategies

• Autorzy: Janusz A. , Klejman A. , Kiryk-Jaskiewicz A. , Gorlewicz A. , Bieganska K. , Jedynak P. , Kaczmarek L. , Konopka W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Active reorganization of extracellular matrix in the brain allows for growth of neuronal dendrites and axons which guarantees successful incorporation of new born neurons into neuronal network during adult neurogenesis in the hippocampus. Activity of surrounding neurons may affect adult neurogenesis. AIM(S): In order to test whether manipulation of CREB dependent gene expression in neurons and hence their activity will influence adult neurogenesis we have developed the Syn-Flag-ICER II transgenic rat line. The ICER (Inducible cAMP Early Repressor) is effective endogenous repressor of CREB/CREM/ATF transcription factors family. METHOD(S): BrdU labeling to asses a level of adult neurogenesis in the hippocampus qPCR for changes in transcription of CREB/CREM and related genes gelatin zymography to measure MMP9 activity Morris Water Maze spatial learning tests Patch Clamp RESULTS: ICER II overexpressing rats showed diminished hippocampal neurogenesis. We have observed a reduced number of mature BrdU positive cells in granular zone of hippocampus of transgenic rats, in comparison to control group. We have observed also that neurons of dentate gyrus demonstrate increased excitability. Paradoxically, we have detected increased levels of mRNA for CREB or CREM factors. Also CREB dependent miR-132 expression was upregulated in transgenic rats, which regulates expression of MMP-9 – extracellular matrix metalloproteinase. We have found the decreased activity of MMP9 in ICER overexpressing rats. Morris Water Maze tests didn’t show overall differences in rats learning and memory capabilities, however male ICER rats chose more often imprecise strategies to find hidden platform than control males. CONCLUSIONS: Obtained results indicate that CREB dependent gene expression in neurons regulates a set of genes e.g. miR-132 that may in turn regulate translation of proteins involved in remodeling of extracellular matrix and affect adult neurogenesis, what changes discrete aspects of animal cognitive behavior.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.126

Twórcy

autor

Janusz A.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Klejman A.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Kiryk-Jaskiewicz A.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Gorlewicz A.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Bieganska K.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Jedynak P.

• Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy

autor

Kaczmarek L.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Konopka W.

• Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland