title: Dysregulated CREB signaling pathway in the brain of neural cell adhesion molecule (NCAM)-deficient mice.
abstract: The neural cell adhesion molecule (NCAM) mediates cell-cell interactions and plays an important role in processes associated with neural plasticity, including learning and memory formation. It has been shown that mice deficient in all isoforms of NCAM (NCAM-/- mice) demonstrate impairment in long-term plasticity at multiple hippocampal synapses, disrupted spatial learning, and impaired contextual and auditory-cued fear conditioning. The formation of long-term memory is associated with activation of transcription factor CREB (cAMP response element binding protein). The aims of this study were to investigate NCAM-mediated signaling transduction pathways and the levels of the phosphorylated (Ser133) active form of the CREB in the brain structures (the pre- and frontal cortex, basolateral amygdala, and hippocampus) involved in the memory formation in NCAM-deficient mice. Immunohistochemical analysis revealed reduced levels of pCREB in the prefrontal cortex (PFC), frontal cortex (FC), CA3 subregion of the hippocampus (CA3) and basolateral nucleus of amygdala (BLA) in NCAM-/- mice. NCAM-/- mice had also reduced levels of the phosphorylated CaMKII and CaMKIV in PFC/FC and the hippocampus, which are the downstream signaling molecules of NCAM. The levels of non-phosphorylated kinases did not differ from those seen in the wild-type mice. These results provide evidence that NCAM deficiency results in the dysregulation of CREB-mediated signaling pathways in the brain regions, which is related to the formation of memory.
authors.affiliation: Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, 19 Ravila Street, 51014, Estonia.
authors.forename: Anu
authors.initials: A
authors.lastname: Aonurm-Helm
authors.forename: Tamara
authors.initials: T
authors.lastname: Zharkovsky
authors.forename: Monika
authors.initials: M
authors.lastname: Jürgenson
authors.forename: Anti
authors.initials: A
authors.lastname: Kalda
authors.forename: Alexander
authors.initials: A
authors.lastname: Zharkovsky
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D019006:Neural Cell Adhesion Molecules; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517685:Camk4 protein, mouse