Genome-wide transcriptome profiling of region-specific vulnerability to oxidative stress in the hippocampus

Abstract

Neurons in the hippocampal CA1 region are particularly sensitive to oxidative stress (OS), whereas those in CA3 are resistant. To uncover mechanisms for selective CA1 vulnerability to OS, we treated organotypic hippocampal slices with duroquinone and compared transcriptional profiles of CA1 vs CA3 cells at various intervals. Gene Ontology and Biological Pathway analyses of differentially expressed genes showed that at all time points, CA1 had higher transcriptional activity for stress/inflammatory response, transition metal transport, ferroxidase, and presynaptic signaling activity, while CA3 had higher GABA-signaling, postsynaptic, and calcium and potassium channel activity. Real-time PCR and immunoblots confirmed the transcriptome data and the induction of OS by duroquinone in both hippocampal regions. Our functional genomics approach has identified in CA1 cells molecular pathways as well as unique genes, such as guanosine deaminase, lipocalin 2, synaptotagmin 4, and latrophilin 2, whose time-dependent induction following the initiation of OS may represent attempts at neurite outgrowth, synaptic recovery, and resistance against OS.

Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria

“…4F–J). Previous literatures reported that releasing progerin from the nuclear membrane by farnesyltransferase inhibitor treatment partially rescued the gene expression and morphological defects in HGPS cells (Capell et al ., 2005, 2008; Capell & Collins, 2006; Gelb et al ., 2006; Cao et al ., 2007; Wang et al ., 2007; Marji et al ., 2010). Indeed, we find that not only the nuclear morphology but also the chromatin organization and gene expression are improved in the MB‐treated HGPS nucleus (Fig.…”

Lipocalin 2: Novel component of proinflammatory signaling in Alzheimer's disease

“…This observation correlates with the finding that cyclooxygenase‐2, which is up‐regulated at sites of inflammation, is also primarily up‐regulated in these neurons (29). Lcn2 mRNA expression was also found to be up‐regulated in area CA1 of the hippocampus in rat after oxidative stress in vivo (54), indicating that Lcn2 is up‐regulated in hippocampus tissue during neuronal injury.…”

Metabolism Changes During Aging in the Hippocampus and Striatum of Glud1 (Glutamate Dehydrogenase 1) Transgenic Mice

“…The rationale for studying metabolite changes in two brain regions was based on our past observations that neurons in adjoining regions of the brain may differ very significantly in terms of gene expression patterns and in their vulnerability to metabolic and oxidative stress, including the stress brought about by the aging process [38, 39, 51, 54–57]. Furthermore, it has previously been shown that the levels of Glu, Gln, GABA and Asp may vary by a factor of five and up to a factor of 21 in different regions of rat brains, and that the effects of aging on the levels of these amino acids are not identical across various rat [58] or mouse brain regions [59].…”