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Publication : Ultrastructural and transcriptional profiling of neuropathological misregulation of CREB function.

First Author  Valor LM Year  2010
Journal  Cell Death Differ Volume  17
Issue  10 Pages  1636-44
PubMed ID  20395962 Mgi Jnum  J:186359
Mgi Id  MGI:5432081 Doi  10.1038/cdd.2010.40
Citation  Valor LM, et al. (2010) Ultrastructural and transcriptional profiling of neuropathological misregulation of CREB function. Cell Death Differ 17(10):1636-44
abstractText  We compare here the neurodegenerative processes observed in the hippocampus of bitransgenic mice with chronically altered levels of cAMP-response element-binding protein (CREB) function. The combination of genome-wide transcriptional profiling of degenerating hippocampal tissue with microscopy analyses reveals that the sustained inhibition of CREB function in A-CREB mice is associated with dark neuron degeneration, whereas its strong chronic activation in VP16-CREB mice primarily causes excitotoxic cell death and inflammation. Furthermore, the meta-analysis with gene expression profiles available in public databases identifies relevant common markers to other neurodegenerative processes and highlights the importance of the immune response in neurodegeneration. Overall, these analyses define the ultrastructural and transcriptional signatures associated with these two forms of hippocampal neurodegeneration, confirm the importance of fine-tuned regulation of CREB-dependent gene expression for CA1 neuron survival and function, and provide novel insight into the function of CREB in the etiology of neurodegenerative processes.
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